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Jun Adachi and Masami Hasegawa have written a package MOLPHY, version 2.3b3, carrying out maximum likelihood inference of phylogenies for either nucleotide sequences or protein sequences. Their protein sequence maximum likelihood program, ProtML, is a successor to the one they made available to me and which I formerly distributed on a nonsupported basis in PHYLIP. The package is distributed free in C source code, with documentation. MOLPHY is available from its web site from http://www.ism.ac.jp/ismlib/softother.e.html   A monograph describing MOLPHY (number 28 in the Computer Science Monographs of the Institute of Statistical Mathematics) is available from the same source (see folder csm96 on the distribution web page), as TeX source and as a .dvi file. The monograph can also be ordered from the Institute. An executable version of MOLPHY 2.2 for Windows95 or Windows NT on Intel processors, and also one that works on Windows NT on DEC Alpha processors, is available from Russell Malmberg at the Botany Department of the University of Georgia (russell  (at) plantbio.uga.edu) at his software web site at http://www.plantbio.uga.edu/~russell/index.php?s=1&n=5&r=0

Gary Olsen, of the Department of Microbiology, University of Illinois, Urbana, Illinois (gary  (at) life.uiuc.edu) has developed a speeded-up replacement for my program DNAML coded in C, called fastDNAml version 1.2.2. It achieves a number of economies and also is organized so that it can be run on parallel processors -- he and his co-workers have constructed trees of very large size on a high-speed parallel processor. The program can be compiled using the "p4" portable parallel processing toolkit. It can also be run in ordinary serial mode on workstations where it is faster than DNAML. fastDNAml is described in a paper: Olsen, G. J., H. Matsuda, R. Hagstrom, and R. Overbeek. 1994. fastDNAml: A tool for construction of phylogenetic trees of DNA sequences using maximum likelihood. Computer Applications in the Biosciences (CABIOS) 10: 41-48. It is available in the following places:

• The C program and MacOS 9 and MacOS X executables are available by ftp from the Indiana University Biology ftp server at ftp.bio.indiana.edu in directory molbio/evolve.
• A Debian Linux executable package for fastDNAml was made available by Stephane Bortzmeyer and is maintained by Andreas Tille. It is available through its web page at http://packages.debian.org/unstable/science/fastdnaml.

Bette Korber of the Theoretical Division, Los Alamos National Laboratory , Los Alamos, New Mexico (btk  (at) t10.lanl.gov) and her colleagues have released a version of fastDNAml which uses the REV (general reversible) model of DNA evolution. They used it for the results in the paper: B. Korber, M. Muldoon, J. Theiler, F. Gao, R. Gupta, A. Lapedes, B. H. Hahn, S. Wolinksy and T. Bhattacharya. 2000. Timing the ancestor of the HIV-1 pandemic strains. Science 288: 1789-1796. The program is available both in a version using the MPI Message-Passing Interface for parallel computers or a non-parallel version. It is available as C source code for Unix from the web site for the programs from that paper at http://www.santafe.edu/~btk/science-paper/bette.html.

Alexandros Stamatakis (alexandros.stamatakis  (at) h-its.org) of the Heidelberger Institut für Theoretische Studien, Heidelberg, Germany and his colleagues have released RAxML, version 7.2.8, a program for faster reconstruction of phylogenies by maximum likelihood. It provides faster heuristic search, use of parallel processing, and a simulated annealing algorithm, RAxML can also carry out parsimony, bootstrapping, and consensus tree methods. There are a number of papers describing RAxML:

• Stamatakis, A., T. Ludwig, H. Meier, and M. J. Wolf. 2002. AxML: A fast program for sequential and parallel phylogenetic tree calculations based on the maximum likelihood method. pp. 21-28 in Proceedings of 1st IEEE Computer Society Bioinformatics Conference (CSB2002), Palo Alto, California, August 2002.
• Stamatakis, A., T. Ludwig, and H. Meier 2003. RAxML-II: A program for sequential, parallel and distributed inference of large phylogenetic trees. Concurrency and Computation: Practice and Experience (CCPE) 16: 975-988.
• Stamatakis, A., T. Ludwig, and H. Meier. 2004. RAxML-III: A fast program for maximum likelihood-based inference of large phylogenetic trees. Bioinformatics Advance Access published on December 17, 2004.

   Daniele Silvestro and Ingo Michalak of the Department of Botany and Molecular Evolution of the Senckenberg Research Institute, Frankfurt am Main, Germany (raxmlgui.help (at) googlemail.com) have released raxmlGUI (RAxML Graphical User Interface), version 1.0, A graphical user interface for RAxML. RaxmlGUI is intended to accelerate and simplify the usage of RAxML, enabling an interactive control of all its major features (as of RAxML version 7.2.8). The graphical interface is designed to be self-explanatory and to make its use very intuitive. In addition, a detailed built-in help file is available. Through the implementation of multi-thread versions of RAxML, the GUI enables the optimal utilization of the available computational resources. It is described in the paper: Silvestro, D. and I. Michalak. 2011. raxmlGUI: a graphical front-end for RAxML. Organisms Diversity & Evolution DOI: 10.1007/s13127-011-0056-0. It is available as Python script and Intel Mac OS X executables. It can be downloaded from its web site at https://sites.google.com/site/raxmlgui/

Thomas Keane (thomas.m.keane (at) nuim.ie) and Thomas Naughton (tom.naughton (at) nuim.ie), both of the Department of Computer Science of the National University of Ireland, Maynooth have released DPRML, a distributed cross-platform tree-building program that can use the idle clock cycles of machines, allowing idle time on hundreds of machines to be harnessed for tree-building. It uses the PAL Java framework. It is described in a paper: Keane, T.M., T. J. Naughton, S. A. A. Travers, J. O. McInerney, and G. P. McCormack. 2005. DPRml: Distributed Phylogeny Reconstruction by Maximum Likelihood. Bioinformatics 21: 969-974. DPRML can be downloaded from its web page at http://distributed.cs.nuim.ie/dprml.php Its authors note that it is slower than their more recent distributed phylogeny platform MULTIPHYL, and they urge use of that instead of DPRML.

T. M. Keane, T.J. Naughton, S.A.A. Travers, J.O. McInerney, and G.P. McCormack, of the Department of Computer Science at the the National University of Ireland, Maynooth, Ireland (tkeane  (at) cs.nuim.ie ) have produced MultiPhyl, version 1.06, a distributed phylogeny platform enabling maximum likelihood runs across a large number of heterogeneous machines. MultiPhyl is a high-throughput implementation of a distributed phylogenetics platform that is capable of using the idle computational resources of many heteogeneous non-dedicated machines to form a phylogenetics supercomputer. It allows a user to upload hundreds or thousands of amino acid or nucleotide alignments simultaneously and perform computationally intensive tasks such as model selection, tree searching, and bootstrapping of each of the alignments. The program implements a set of 80 amino acid models and 56 nucleotide ML models and a variety of statistical methods for choosing between alternative models. It is described in the paper: Keane, T.M., T.J. Naughton, S.A.A. Travers, J.O. McInerney, and G.P. McCormack. 2005. DPRml: Distributed Phylogeny Reconstruction by Maximum Likelihood. Bioinformatics 21(7): 969-974. It is available as Java code. It can be downloaded from the downloads web site at http://distributed.cs.nuim.ie/downloads.php for the distributed Java-based platform produced by this group. The platform itself can also be downloaded from the same site. Multiphyl can also be tested by using their web server version.

Ziheng Yang of the Department of Genetics and Biometry, University College London, (z.yang  (at) ucl.ac.uk) has released PAML, version 4.4, a package of programs for the maximum likelihood analysis of nucleotide or protein sequences, including codon-based methods that take into account both amino acids and nucleotides. The programs can estimate branch lengths in a phylogenetic tree and parameters in the evolutionary model such as the transition/transversion rate ratio, the gamma parameter for variable substitution rates among sites, rate parameters for different genes, and synonymous and nonsynonymous substitution rates. They can also test evolutionary models, calculate substitution rates at particular sites, reconstruct ancestral nucleotide or amino acid sequences, simulate DNA and protein sequence evolution, compute distances based on the synonymous and nonsynonymous changes, and of course do phylogenetic tree reconstruction by maximum likelihood and Bayesian Markov Chain Monte Carlo methods. The strength of the package lies in its rich implementation of evolutionary models, though Yang coments that tree-making is not a strong point of the current version. Another notable point is the availability of codon models, which Yang pioneered. The package is available as Windows executables and as C source code for Unix and MacOS X systems. An Old Versions folder in the ftp site that distributes these also contains Mac OS executables for the earlier versions 3.0a and 3.0c. See the PAML web page at http://abacus.gene.ucl.ac.uk/software/paml.html where it is available.

   Amy Egan and Joana Silva of The Institute for Genomic Research (TIGR) in Rockville, Maryland (aegan (at) jcvi.org) have produced IDEA (Interactive Display for Evolutionary Analysis), version 2.4, a graphical interface for PAML. IDEA allows you to run either of the PAML programs codeml or baseml on a single dataset or on multiple datasets simultaneously. They allow you to obtain maximum likelihood estimates of numbers of substitutions per branch and per site and to compare multiple models of molecular evolution given the data and a phylogenetic tree for the sequences. You can optionally generate phylogenies with PHYLIP, using maximum parsimony (on small datasets) or neighbor-joining. IDEA can perform multiple runs of codeml with different starting (dN/dS) values and merge their results for increased accuracy. It can also analyze multiple datasets in parallel and save parameter values for future use, and monitor progress step by step. For codeml analyses of sites-based evolutionary models features an interactive tabular summary of results, visualizations of selective pressure along genes, interactive histograms and depictions of phylogenetic trees with branch lengths proportional to the estimated number of nucleotide substitutions. It is available as a combination of Perl script, Java executables and Linux or Solaris executables. It can be run on systems that have Perl, Java, PAML 3.14 or 3.15, and PHYLIP. If parallel execution is desired you need to have SGE or Condor, otherwise it will just run on the machine on which it is launched. It can be downloaded from its web site at http://ideanalyses.sourceforge.net/main.html

Tim Massingham and Nick Goldman of the Eurpean Bioinformatics Institute in Hinxton, U. K. (timm (at) ebi.ac.uk and goldman (at) ebi.ac.uk) have produced SLR (Sitewise Likelihood Ratio), a program to compute and test the nonsynonymous/synonymous ratio of substitutions at each site. For coding sequences it makes a maximum likelihood estimate for each amino acid position of the ratio of nonsynonymous substitutions to synonymous substitutions, and does a likelihood ratio test for that site. The many sitewise tests are then corrected for multiple comparisons to indicate which sites have strong evidence of purifying or positive selection and so whether there is any reliable evidence for the presence of selection in the alignment. Alternatively SLR can restricted to only detect unusually variable sites, indicating such sites and providing evidence for the presence of positive selection in the alignment. It is described in the paper: Massingham, T. and N. Goldman. 2005. Detecting amino acid sites under positive selection and purifying selection. Genetics 169: 1853-1762. It is available as C source code, Windows executables, Linux executables and Powermac Mac OS X executables. It can be downloaded from its web site at http://www.ebi.ac.uk/goldman/SLR/

  Gangolf Jobb (gangolf (at) treefinder.de), formerly of the Institut für Statistik of the University of München, Germany, has produced Treefinder, a maximum likelihood program for nucleotide sequence data. It makes available a variety of models of base change, including codon-position-specific models. It carries out search for best trees by its own method of tree rearrangement, and can assess statistical support for groups by either bootstrap or a local paired-sites method. All parameters of the models can be optimized by searching for the values that maximize the likelihood. The program is fast, and has both a graphical user interface and a general language in which its operation can be programmed. Trees can be interactively manipulated and constrained in various ways. Treefinder is described in a paper: Jobb, G., A. von Haeseler, and K. Strimmer. 2004. TREEFINDER: A powerful graphical analysis environment for molecular phylogenetics. BMC Evolutionary Biology 4: 18. It has been available for download from its web site at http://www.treefinder.de as executables for Windows, Mac OS X, and Linux. It requires the Java runtime environment to be present. However currently Jobb has declared himself "on strike" at this web site and asks that people first email him to discuss whether he should be compensated for his work. I do not know whether that means that the program is available for free currently, or whether he will soon start charging for it. He certainly deserves compensation for this good program.

Stéphane Guindon (currently at the University of Auckland, New Zealand, s.guindon  (at) auckland.ac.nz) and Olivier Gascuel (gascuel (at) lirmm.fr) at the LIRMM, of the CNRS and the University of Montpellier II, France, have released PHYML version 3.0, a fast maximum likelihood program for nucleotide or protein sequence data. It has 6 possible DNA substition models, 5 amino acid substitution models, allowing estimation of many of the model parameters, and can allow for a gamma distribution of rates among sites and a proportion of invariable sites. It can also do bootstrapping of the trees. PHYML is described in a paper: Guindon, S., and O. Gascuel. 2003. A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Systematic Biology 52: 696-704. It is available as Linux, SunOS, Windows, and Mac OS X executables from its web site in Montpellier at http://www.atgc-montpellier.fr/phyml/binaries.php, where it is also available as a web server.

Johan Nylander (Johan.Nylander  (at) abc.se) has written BootPHYML version 3.4. This is a Perl script that performs bootstrapping using programs from PHYLIP , substituting PHYML for the PHYLIP program DNAML. It works with Mac OS X and Linux or Unix. It is available on a web page at Nylander's web site in Sweden.

Bastien Boussau of the Laboratoire de Biométrie et Biologie Evolutive of the Université Lyon 1, CNRS, Lyon (bastien.boussau (at) univ-lyon1.fr) has released nhPhyML (non-homogeneous PhyML), version 1.00, a program based on PHYML to reconstruct trees with a non-homogeneous model of DNA sequence evolution. nhPhyML can reconstruct phylogenies by Maximum Likelihood framework using the Galtier and Gouy (1998) nonhomogenous model of DNA sequence evolution. This model allows different equilibrium G+C content to be associated to different branches of the phylogeny. nhPhyML will locally rearrange a given rooted phylogeny without changing the root position, and will optimize parameters of the model of sequence evolution. It is described in the paper: Boussau, B., and M. Gouy. 2006. Efficient likelihood computations with nonreversible models of evolution. Systematic Biology 55 (5): 756-768. It is available as C source code and Linux executables. It can be downloaded from its web site at http://pbil.univ-lyon1.fr/software/nhphyml/

Bastien Boussau of the Laboratoire de Biométrie et Biologie Evolutive of the Université Lyon 1, CNRS, Lyon (bastien.boussau (at) univ-lyon1.fr) has released PhyML-Multi (a PhyML-derived program to detect recombination which uses multiple trees for one alignment), version 1.00, a program that can infer recombination breakpoints and infer multiple phylogenetic from one alignment. PhyML-Multi can find recombination breakpoints in an alignment and infer phylogenies. It takes as input a sequence alignment and a putative number k of trees to reconstruct. Then, using a HMM or a mixture model, it will infer k trees from the alignment and predict recombination breakpoints, under the Maximum Likelihood criterion. PhyML-Multi can work on DNA sequences as well as protein sequences, and can handle dozens of sequences. It is described in the paper: Boussau, B., L. Guéguen, and M. Gouy. 2009. A mixture model and a hidden markov model to simultaneously detect recombination breakpoints and reconstruct phylogenies. Evolutionary Bioinformatics Online 5 (June 25): 67-79. It is available as C source code and Linux executables. It can be downloaded from its web site at http://pbil.univ-lyon1.fr/software/phyml_multi/

Pierre Rioux and Tim Littlejohn, then of the Informatics Division of the Organelle Genome Megasequencing Program at the Université de Montréal (LittleJohn is currently at BioLateral Group, in Sydney, Australia, tim  (at) biolateralgroup.com) made available PARBOOT (PARallel BOOTstrapping), a program that takes bootstrap sampled data sets and splits them up, submitting each to a different computer, so as to run bootstrapping quickly on networks of computers. It is intended for use with PHYLIP programs. It is available free as C source code from the Indiana University IUBIO software archive at http://microbe.bio.indiana.edu:7131/soft/iubionew/molbio/evolution/phylo/ParBoot/. It is no longer available by ftp from Montréal. It is described on a web page at the Université de Montréal at http://megasun.bch.umontreal.ca/aboutpb.html. It requires a networked system of computers with PHYLIP, a Perl interpreter, and appropriate accounts and permissions.

Laura Salter Kubatko of the Departments of Statistics and Evolution, Ecology, and Organismal Biology at the Ohio State University, Columbus, Ohio (lkubatko (at) stat.ohio-state.edu) has written SSA (inference of maximum likelihood phylogenetic trees using a Stochastic Search Algorithm), version 1.0 , a program that uses a stochastic search to find maximum likelihood phylogenies. SSA is a program for inferring maximum likelihood phylogenies from DNA sequences. Two versions of the program are available: one which assumes a molecular clock and one which does not make this assumption. The method for searching the space of trees for the ML tree is based on a simulated-annealing type algorithm. The program implements the F84 model of nucleotide substitution and associated sub-models. It estimates the ML tree and branch lengths, and can optionally estimate the transversion/transversion ratio. Upon termination, the program returns the k trees of highest likelihood found during the search, where k can be set by the user. It is described in the paper: Salter, L. A. and D. K. Pearl. 2001. Stochastic search strategy for estimation of maximum likelihood phylogenetic trees. Systematic Biology 50(1): 7-17. It is available as executables for Windows, Linux, AIX, and SPARC systems. Laura is also willing to send the source code to users who own the book Numerical Recipes in C by Press, Teukolsky, Vetterling and Flannery, and who thus have permission to use routines from that book. The documentation and executables can be downloaded from its web site at http://www.stat.ohio-state.edu/~lkubatko/software/ssa/ssa.html

Nir Friedman, Matan Ninio, Tal Pupko, Eval Privman, and Itshak Pe'er of the Department of Computer Science and Engineering of Hebrew University, Jerusalem, Israel, and the Department of Cell Research and Immunology of Tel Aviv University, Israel (semphy (at) cs.huji.ac.il) have written SEMPHY (Structural EM PHYlogenetic reconstruction), version 2.0, Uses the structural EM algorithm to search for maximum likelihood phylogenies. The Structural EM algorithm is one proven to go uphill on the likelihood surface, and should gain in efficiency and adequacy of search of the likelihood surface compared to other likelihood algorithms. The program can use DNA or protein sequences, and can use a variety of DNA models and amino acid replacement models including the general reversible model and the HKY model (for DNA) and the JTT model (for protein sequences). It also allows for Gamma-distributed among-sites rate variation. SEMPHY also makes available an iterative distance matrix method which computes Bayesian posterior rates of change at individual sites, uses these to compute distances and find a neighbor-joining tree. The program and methods are described in the papers:

• Friedman, N., M. Ninio, I. Pe'er, and T. Pupko. 2002. A Structural EM Algorithm for phylogenetic inference. Journal of Computational Biology 9(2): 331-353.
• Ninio, M., E. Privman, T. Pupko, and N. Friedman. 2007. Phylogeny reconstruction: increasing the accuracy of pairwise distance estimation using bayesian inference of evolutionary rates. Bioinformatics 23: e136-e141.

Simon Whelan of the Faculty of Life Sciences at the University of Manchester, U.K. (simon.whelan (at) manchester.ac.uk) has released Leaphy (Likelihood Estimation Algorithms for PHYlogenetics), version 1.0beta, a fast and accurate program for maximum likelihood phylogenetic inference. Leaphy uses maximum likelihood to estimate trees from aligned amino acid and nucleotide sequences under a variety of commonly used and popular models. The methods for searching for the best tree topology are described in the paper: Whelan, S. 2007. New approaches to phylogenetic tree search and their application to large numbers of protein alignments. Systematic Biology 56: 727-740. It is available as Windows executables and Linux executables. It can be downloaded from its web site at http://www.bioinf.manchester.ac.uk/leaphy/Leaphy.htm

Daniele Catanzaro of the Computer Science Department of the Université Libre de Bruxelles (U.L.B.) (dacatanz (at) @ulb.ac.be) has released PhyloCoco version 2.3, a molecular phylogeny package for Intel-iMac with OS 10.4.9 or higher and Java 1.4 or higher. PhyloCoco is a minimalist tool for rebuilding molecular phylogenies by means of the likelihood criterion or the minimum evolution criterion. Phylococo selects the best substitution model of DNA evolution for the dataset of sequences to be analyzed and displays the best phylogeny found so far. It uses the GTR model of DNA evolution and uses different optimization methods including the Very Large Scale Neighborhood (VLSN) search for the topology and Iterated Local Search (ILS) to explore the solution space. PhyloCoCo uses FigTree to display the resulting phylogeny. It is described in the paper: Catanzaro, D., R. Pesenti and M. C. Milinkovitch. 2007. Estimating phylogenies under maximum likelihood: a very large-scale neighborhood approach. Submitted to BMC Bioinformatics. It is available as Java source code and Intel Mac OS X executables. It can be downloaded from its web site at http://homepages.ulb.ac.be/~dacatanz/Site/PhyloCoco.html

  Vivek Gowri-Shankar and Howsun Jow (vivek.gowri-shankar (at) s.man.ac.uk) of the Department of Computer Sciences of the University of Manchester, Manchester, U.K. have written PHASE, version 1.1, a software package for PHylogenetics And Sequence Evolution. It infers phylogenies with models for RNA evolution that include models for both paired sites and unpaired sites. The models for the unpaired sites have the usual 4 states, while the models for the paired sites have 6, 7, or 16 states, depending on the model chosen. The programs carry out a Bayesian Markov chain Monte Carlo (MCMC) analysis that samples trees from the posterior distribution given the data. PHASE is described in two papers:

• Hudelot, C., V. Gowri-Shankar, H. Jow, M. Rattray and P. Higgs. 2003. RNA-based phylogenetic methods: Application to mammalian mitochondrial RNA sequences. Molecular Phylogenetics and Evolution 28: 241-252.
• Jow, H., C. Hudelot, M. Rattray and P. Higgs. 2002. Bayesian phylogenetics using an RNA substitution model applied to early mammalian evolution. Molecular Biology and Evolution 19: 1591-1601.

Le Sy Vinh (vinh  (at)  cs.uni-duesseldorf.de) and Heiko Schmidt (heiko  (at)  cs.uni-duesseldorf.de) of the Institut für Bioinformatik of the University of Düsseldorf, Germany and Arndt von Haeseler (arndt.von.haeseler  (at)  univie.ac.at) of the Center for Integrative Bioinformatics Vienna (CIBIV), Austria, have written Phylogenetic Navigator (PhyNav) version 1.0. This program finds subsets of species in a dataset that are "minimal k-distance subsets" and analyses these each by maximum likelihood. Then it stitches these groups together using likelihood. This makes it possible to analyze larger datasets. The program is described in a paper: Vinh, L. S., H. A. Schmidt, and A. von Haeseler. 2005. PhyNav: A novel approach to reconstruct large phylogenies. pp. 386-393 in Classification, the Ubiquitous Challenge (Proceedings of the 28th Annual Conference of the GfKl 2004), ed. C. Weihs and W. Gaul. Series Studies in Classification, Data Analysis, and Knowledge Organization. Springer-Verlag, Heidelberg/New York. It is available as Linux executables from its web site at http://www.cibiv.at/software/phynav/

  Shu-chuan (Grace) Chen of the School of Mathematical and Statistical Sciences of Arizona State University, Tempe, Arizona (shu-chuan.chen (at) asu.edu) has released MixtureTree version 2.0, A phylogenetic tree package based on mixture models for reconstructing phylogeny from binary sequence data. MixtureTree is a Linux based program (written in C/C++) which implements an algorithm for binary sequence data, such as single-nucleotide polymorphisms (SNPs). In addition to the mixture algorithm with three different optimization options, the program also implements a bootstrap procedure with a majority-rule consensus tree. The program is described in the papers:

• Chen, S. C., M. Rosenberg, and B. Lindsay. 2011. MixtureTree: a program for constructing phylogeny, BMC Bioinformatics 12: 111.
• Chen, S. C., M. Li, M. Rosenberg, and B. Lindsay. 2011. Mixture tree construction and its applications. pp 135-147 in pp. 135-147 in Handbook of Statistical Bioinformatics, ed. by H. S. Lu, B. Scholkopf, and H. Zhao. Springer Handbooks of Computational Statistics. Springer-Verlag

Morgan Price of the Adam Arkin's group in the Physical Biosciences Division of Lawrence Berkeley National Laboratory, Berkeley, California (fasttree (at) microbesonline.org) has produced FastTree version 2, a fast maximum likelihood program that starts from a neighbor-joining-like distance matrix estimate of the tree, which is inferred using profiles of sequences instead of a distance matrix. It then rearranges that tree using a minimum evolution criterion, and finally optimizes the tree by nearest-neighbor rearrangements using likelihood as the criterion. The final tree is thus at least a local optimum using likelihood. It is described as having run times proportional to N²L, where N is the number of species and L the sequence length. It can handle either nucleotide or protein sequences. It also computes a measure of local support for nodes using bootstrapping and a Shimodaira-Hasegawa (SH) method involving nearby nodes. It can use multithreading to take advantage of multiple processors. It is described as much faster than other likelihood programs. FastTree uses a GTR model of substitution, with gamma-distributed rate variation. It is described in two papers:

• Price, M. N., P. S. Dehal, and A. P. Arkin 2009. FastTree: Computing large minimum-evolution trees with profiles instead of a distance matrix. Molecular Biology and Evolution 26: 1641-1650
• Price, M. N., P. S. Dehal, and A. P. Arkin 2010. FastTree 2 -- approximately maximum-likelihood trees for large alignments. PLoS ONE 5(3): e9490

Paul Michael Agapow, then of the Department of Biology of Imperial College, Silwood Park, U.K. and more recently of the Health Protection Agency, U.K., (agapow (at) agapow.net) has written Mac5, version 1.7.3, a program for phylogenetic reconstruction using gapped data. MAC5 implements MCMC sampling to estimate a phylogenetic tree from a DNA multiple alignment. What differentiates MAC5 from similar programs is its use of five-state sequence evolution models as a means to include the gap information. It is available as C source code, Windows executables and Powermac Mac OS X executables. Its author says that owing to other projects, Mac5 is not being further developed and is not being supported by him. It can be downloaded from its web site at http://www.agapow.net/software/mac5

David Posada (dposada  (at) uvigo.es) of the Department of Biochemistry, Genetics and Immunology of the University of Vigo, Spain and Keith Crandall of the Department of Biology, Brigham Young University released Modeltest version 3.7, a program to test a hierarchy of statistical models of DNA evolution using the Likelihood Ratio Test criterion and the AIC (Akaike Information Criterion). The likelihood values are obtained by running PAUP*. MODELTEST accepts likelihood scores corresponding to 56 models of DNA substitution including whether transition and transversion rates are equal, whether rates at different sites are equal, and whether there are invariant sites. Modeltest is described in the paper: Posada, D. and K. A. Crandall. 1998. MODELTEST: testing the model of DNA substitution. Bioinformatics 14: 817-818. It is available as executables for Macintosh, for Windows, and source code in C for that can be compiled on many other systems. It is distributed from its web site at http://darwin.uvigo.es/software/modeltest.html. Modeltest was the basis for two further developments: the MrModeltest program which uses MrBayes and the FindModel server at Los Alamos National laboratories which is a revised version of Modeltest that uses the weighbor program to infer the trees.

David Posada (dposada  (at) uvigo.es) of the Department of Biochemistry, Genetics and Immunology of the University of Vigo, Spain has released jMODELTEST version 0.1.1, a Java version of Modeltest. Like Modeltest, it carries out statistical selection of best-fit models of nucleotide substitution. It implements five different model selection strategies: hierarchical and dynamical likelihood ratio tests (hLRT and dLRT), Akaike and Bayesian information criteria (AIC and BIC), and a decision theory method (DT). It also provides estimates of model selection uncertainty, parameter importances and model-averaged parameter estimates, including model-averaged phylogenies. It is described in the paper: Posada D. 2008. jModelTest: Phylogenetic Model Averaging. Molecular Biology and Evolution 25: 1253-1256. It is distributed as Java executables that will run on Java-equipped Windows systems, on Mac OS X, and on Linux systems that have Java installed. It also uses PHYML to comput maximum likelihood trees under the various models. I do not know whether it comes with PHYML installed or requires the user to install it. jMODELTEST will be found at its web site at http://darwin.uvigo.es/software/jmodeltest.html

Paulo Nuin (nuinp  (at) mcmaster.ca) of the Department of Biology, McMaster University, Hamilton, Ontario, Canada has released MrMTgui version 1.01. This is a graphic user interface for running Modeltest and MrModeltest. It is available for Windows as executables from the MrMTgui web site at http://genedrift.org/mtgui.php. Source code of a Linux version is also available which can be compiled using the WxWindows windowing software. The Linux sources are available by accessing a svn (subversion) version-control code base, using instructions available at the above site. MrMTgui was formerly known as MTgui in the earlier version which could not access MrModeltest.

Johan Nylander (Johan.Nylander  (at) abc.se) has released MrModeltest version 2.2. This is a program which is a simplified version of Modeltest 3.7. It is performs hierarchical likelihood ratio tests and calculates approximate AIC, AICc, and Akaike weights of the nucleotide substitution models currently implemented in both PAUP* and MrBayes. Version 2 has added use of four different hierarchies for the likelihood ratio tests and the selected model being printed in a MrBayes block. MrModeltest is available as an executable and source code for Windows, for Mac OS, and for Mac OS X, and as source code for Linux and Unix. It is available from Nylander's software download site at http://www.abc.se/~nylander/ in Sweden.

Johan Nylander (Johan.Nylander  (at) abc.se) has written Modelfit version 1.2, and MrModelfit version 1.2. These are Perl scripts that can run (respectively) Modeltest and MrModeltest simply by typing a single command line. They are available from Nylander's software download site at http://www.abc.se/~nylander/ in Sweden.

Charles Bell of the Department of Biology of Xavier University of Louisiana, New Orleans (cbell3  (at) xula.edu) has written Porn* (Phylogenetics On Rick's Network, as it was originally hosted on Rick Ree's site) verson 2.0, a Linux clone of Modeltest using the Python language. It enables command-line computations equivalent to Modeltest under the Linux operating system. It creates command blocks for PAUP* which can be used when running PAUP*. Porn* is written as a shell script invoking Python modules. It is available at its web site at http://www.phylodiversity.net/cbell/pornstar/

  David Posada (dposada  (at) uvigo.es) of the Department of Biochemistry, Genetics and Immunology of the University of Vigo, Spain has released ProtTest, version 2.4, a Java program allowing testing of 64 different models of protein evolution, using the AIC, AICc, and BIC criteria for choosing among models that include different substitution models, invariant sites, rate heterogeneity, and empirical amino acid frequency variants of the models. ProtTest uses the PAL library of phylogenetic java routines and also uses the PHYML program to compute likelihoods. It is described in the paper: Abascal, F., R. Zardoya and D. Posada. 2005. ProtTest: Selection of best-fit models of protein evolution. Bioinformatics 21: 2104-2105. It is available from its web site at http://darwin.uvigo.es/software/prottest.html

Thomas Keane, of the Bioinformatics and Pharmacogenomics Lab of the Department of Biology, National University of Ireland, Maynooth (thomas.m.keane (at) nuim.ie) has written ModelGenerator, version 0.85. It is a Java program for model selection that selects amino acid and nucleotide substitution models using Fasta or PHYLIP alignments. It supports 56 nucleotide and 80 amino acid substitution models. It is described in the paper: Keane, T. M., C. J. Creevey, M. M. Pentony, T. J. Naughton and J. O. McInerney. 2006, Assessment of methods for amino acid matrix selection and their use on empirical data shows that ad hoc assumptions for choice of matrix are not justified. BMC Evolutionary Biology 6: 29. It is available from its web site at http://bioinf.may.ie/modelgenerator/.

Johan Nylander (Johan.Nylander  (at) abc.se) has written MrAIC verion 1.4.4. This is a Perl script that carries out AIC, AICc, BIC, and Akaike weights model comparison methods for nucleotide substitution models by invoking the PHYML program. It is distributed from Nylander's software download site at http://www.abc.se/~nylander/ in Sweden.

Vladimir Minin, Zaid Abdo, Paul Joyce, and Jack Sullivan of the Department of Biological Sciences at the University of Idaho, Moscow, Idaho (jacks (at) uidaho.edu) or (vminin (at) u.washington.edu) (Minin is now at the University of Washington) have released DT-ModSel (Decision Theory MODel SELection), a performance-based method for selecting a likelihood model for phylogenetic estimation . It implements a model selection method which is based on the Bayesian Information Criterion, but incorporates relative branch-length error as a performance measure in a decision theory (DT) framework. This DT method includes a penalty for overfitting, is applicable prior to running extensive analyses, and simultaneously compares all models being considered and thus does not rely on a series of pairwise comparisons of models to traverse model space. It can compare 56 different models of molecular sequence evolution on a given tree. Minin, V., Z. Abdo, P. Joyce, and J. Sullivan. 2003. Performance-based selection of likelihood models for phylogeny estimation. Systematic Biology 52: 674-683. It is available as Perl script. It can be downloaded from its web site at http://www.webpages.uidaho.edu/~jacks/DTModSel.html

Sergei Kosakovsky Pond and Simon Frost of the Anitviral Research Center, University of California, San Diego and Spencer Muse of the Department of Statistics, North Carolina State University, Raleigh, North Carolina (muse  (at) stat.ncsu.edu) have released HY-PHY (HYpothesis testing using PHYlogenies), version 0.99Beta. HY-PHY has general ways of enabling the user to perform a wide variety of statistical tests of different models of molecular sequence change. It is actually a higher-level programming language which enables the user to set up many different kinds of tests. The user can define their own alphabet of symbols and test any reversible subtitution model. Examples of tests that can be performed include molecular clock tests, relative rate tests, relative ratio tests, and tests of positive selection. It is described in a paper: Kosakovsky Pond, S. L., S. D. Frost, and S. V. Muse. 2005. HyPhy: hypothesis testing using phylogenies. Bioinformatics 21(5): 676-679.

Although not primarily intended as a phylogeny estimation package, it also can infer trees by Neighbor-Joining and UPGMA methods, and a number of search strategies are also available for likelihood inference. HY-PHY is freely available as executables for Mac OS, for Mac OS X, for Windows, and as source code for for Unix and Linux. It is available at the HY-PHY web page at http://www.hyphy.org.

Akifumi S. Tanabe of the Division of Ecology and Evolutionary Biology, Department of Environmental Life Sciences, Graduate School of Life Sciences of Tohoku University, Japan (astanabe (at) mail.tains.tohoku.ac.jp) has released Kakusan4, a parallelized nucleotide substitution model selection script written in the Perl language for data sets with multiple partitions. Kakusan3 supports nucleotide substitution model selection on each partition and/or each codon position by AIC, AICc or BIC. Because the optimization of likelihoods is executed using BASEML, PAUP* or Treefinder and these can be run in parallel, Kakusan can take advantage of multi-core systems or multiple processor systems. The Kakusan Perl script can be run on Windows, MacOS X, Linux, FreeBSD and on other UNIX operating systems. It accepts several different input file formats. It outputs configuration files for Treefinder, MrBayes and PAUP*. It is described in the paper: Tanabe, A. S., 2007, Kakusan: a computer program to automate the selection of a nucleotide substitution model and the configuration of a mixed model on multilocus data. Molecular Ecology Notes 7: 962-964. It is available as Perl script, Windows executables and Mac OS X universal executables. It can be downloaded from its web site at http://www.fifthdimension.jp/products/kakusan/. Earlier versions, Kakusan, Kakusan2, and Kakusan3 can also be downloaded there.

  Jonathan Bollback of the University of Edinburgh, Edinburgh, U.K., and of the Institute of Science and Technology, Austria (j.p.bollback  (at) ed.ac.uk) has written MAPPS (Model Adequacy in Phylogenetics by Predictive Simulation) version 1.1.6, a program to evaluate the fit of a group of phylogenetic models to DNA sequence data. The rationale behind this approach is that an adequate model should be able to predict future data (nucleotide site patterns). In the absence of future data the model's predictive ability is compared to the original data set. The model's predictive ability is evaluated through simulation under the model. Comparison of simulated (or predictive) data sets is evaluated using the multinomial test statistic. The program uses data and trees in a format compatible with the output from MrBayes. It is described in the paper: Bollback, J. P. 2002. Bayesian model adequacy and choice in phylogenetics. Molecular Biology and Evolution 19(7): 1171-1180. It is available as Mac OS X universal executables. It can be downloaded from its web site at http://www.simmap.com/bollback/software.html

Hidetoshi Shimodaira ("Shimo") of the Department of Mathematical and Computing Sciences, Tokyo Institute of Technology, Japan (shimo  (at) is.titech.ac.jp) has released CONSEL version 0.1k, a package of small programs to calculate P values for tests of phylogenies. It uses output from other phylogeny programs (in particular it can use output from PAUP, PAML, PHYML, and MOLPHY) which makes available to it the sitewise log-likelihoods for some trees and the trees themselves. It uses these to carry out the Kishino-Hasegawa test, the Shimodaira-Hasegawa test, a weighted version of the SH test, and a new "approximately unbiased" test of Shimodaira's. CONSEL is available as C source code that will compile on Linux and Unix systems that have the gcc compiler, and it is also available as a DOS executable that will run on DOS or Windows systems. It can be downloaded from its web site at http://www.ism.ac.jp/~shimo/prog/consel/index.html. It is described in a paper: Shimodaira, H. and M. Hasegawa. 2001. CONSEL: for assessing the confidence of phylogenetic tree selection. Bioinformatics 17: 1246-1247 which cites the statistical papers describing the methods.

Hidetoshi Shimodaira ("Shimo") of the Department of Mathematical and Computing Sciences of the Tokyo Institute of Technology, Ookayama, Meguroku, Tokyo, Japan ( shimo (at) is.titech.ac.jp) has written scaleboot (approximately unbiased P-values via multiscale bootstrap), version 0.3-2, an R package for making approximately unbiased P values for tree topologies. savelboot implements Shimodaira's Approximately Unbiased method of putting P values on regions of parameter space, including tree topologies. The P-values are computed from a set of multiscale bootstrap probabilities , computed by sampling different fractions of the characters. The multiscale bootstrap method has also been implemented in the program CONSEL as well. scaleboot has an interface for the pvclust clustering package in R. It also has a front end for phylogenetic inference, and it can replace the CONSEL program for testing phylogenies. Currently, scaleboot does not have a method for file conversion from other phylogeny packages, so we must use CONSEL for this purpose before applying scaleboot to calculate an improved version of AU p-values for trees and branches. The methods are described in the papers:

• Shimodaira, H. 2002. An approximately unbiased test of phylogenetic tree selection, Systematic Biology 51 492-508.
• Shimodaira, H. 2004. Approximately unbiased tests of regions using multistep-multiscale bootstrap resampling, Annals of Statistics 32 2616-2641.

Maria Anisimova, Olivier Gascuel, and Jean-François Dufayard of the Laboratoire d'Informatique, de Robotique et de Microélectronique de Montpellier (LIRMM) of the Université de Montpellier II, Montpellier, France (manisimova (at) hotmail.com) have produced PHYML-aLRT (PHYML approximate Likelihood Ratio Test), version 1.1, a program to carry out likelihood ratio tests of the presence of branches in a phylogeny. PHYML-aLRT is a modification of the original PHYML program, and is designed to compute test of the reality of branches in a known phylogeny. Five branch support tests are available: (1) the bootstrap, (2) aLRT statistics, (3) aLRT parametric (Chi²-based) branch support, (4) aLRT non-parametric branch support based on a Shimodaira-Hasegawa-like procedure, and (5) a combination of these two latters supports, that is, the minimum value of both. The methods are described in the paper: Anisimova, M., and O. Gascuel. 2006. Approximate likelihood ratio test for branchs: A fast, accurate and powerful alternative. Systematic Biology 55(4): 539-552. It is available as Windows executables, Linux executables, Solaris executables, Powermac Mac OS X executables and Intel Mac OS X executables. It can be downloaded from its web site at http://atgc.lirmm.fr/phyml/alrt/ This program was of temporary usefulness; the method was made available in PHYML 3.0 and should probably be used from that program, athough these executables are still available for download.

  Nick Grassly, of the Department of Infectious Disease Epidemiology of the School of Public Health, Imperial College School of Medicine, St. Mary's Campus, London (n.grassly (at) imperial.ac.uk) has written PLATO, version 2.11, (Partial Likelihoods Assessed Through Optimisation), a program that takes sequential PHYLIP-style DNA sequences followed by their maximum likelihood phylogeny, and using a likelihood approach with sliding window analysis and Monte Carlo simulation of the null distribution detects anomalously evolving regions in the DNA sequences and assesses their significance. This may lead to the detection of, for example, recombination, gene conversion or convergence, or reveal variable selective pressures along the gene sequence. A general substitution model is used that can allow the test to reveal differences due to recombination while ignoring those due to varying rate of evolution. The method is described in the paper: Grassly, N. C., and E. C. Holmes. 1997. A likelihood method for the detection of selection and recombination using sequence data. Molecular Biology and Evolution 14: 239-247. It is available as a Mac OS Macintosh binary executable, or in source code for Unix systems. Although no longer distrubuted by Grassly, it is available at the IUBIO web site at http://microbe.bio.indiana.edu:7131/soft/iubionew/molbio/dna/analysis/Plato/

   Iain Milne, Dominik Lindner, and Frank Wright of Biomathematics and Statistics Scotland at the Scottish Crop Research Institute, Invergowrie, Dundee, Scotland (help (at) topali.org) have released TOPALi version 2, a program for statistical and evolutionary analysis of multiple sequence alignments. It is currently at version 2.5. It checks for evidence of past recombination events by looking for changes in the inferred phylogenetic tree TOPology between adjacent regions of a multiple sequence ALignment. Their method detects recombinations by sliding a window along a sequence alignment, and measuring the discrepancy between the trees suggested by the first and second halves of the window, using distance matrix methods. Version 2 includes further statistical tests for recombination based on nonparametric bootstrapping and allowing for rate heterogeneity between sites. It can also launch a range of statistical and evolutionary analyses of multiple sequence alignments as web services running (either locally on your PC) or on the HPC cluster in Dundee. These include phylogenetic model selection (via ModelGenerator), Bayesian and maximum Likelihood phylogenetic tree estimation (via PHYML and MrBayes), detection of sites under positive selection (using PAML), and the recombination breakpoint location analysis methods. The versions of TOPALi are described in two papers:

• Milne, I., D. Lindner, M. Bayer, D. Husmeier, G. McGuire, D. F. Marshall and F. Wright. 2009. TOPALi v2: a rich graphical interface for evolutionary analyses of multiple alignments on HPC clusters and multi-core desktops. Bioinformatics 25 (1): 126-127
• Milne, I., F. Wright, G. Rowe, D. F. Marshal, D. Husmeier, and G. McGuire. 2004. TOPALi: Software for automatic identification of recombinant sequences within DNA multiple alignments. Bioinformatics 20 (11): 1806-1807.

Kim Fisker, then of the Computer Science Department at Aarhus University, Denmark released RecPars, which does a parsimony analysis of DNA sequences. It was more recently maintained by Thomas Christensen of that department. It tries to find the best phylogenies for different regions of the sequences and thereby postulating a recombination event between these segments. The method is described in a paper: Hein, J. 1993. A heuristic method to reconstruct the history of sequences subject to recombination. Journal of Molecular Evolution 36: 396-406. RecPars is available as C source code for Unix. It is distributed from its web site at http://www.daimi.au.dk/~compbio/recpars/recpars.html. A web server is available there as well.

Dan Gusfield (gusfield  (at) cs.ucdavis.edu) and Ren-Hua Chung (rchung  (at) ucdaavis.edu), both of the Department of Computer Science at the University of California, Davis, have released PPH (Perfect Phylogeny Haplotyper). PPH takes a set of diploid genotypes for SNP (single nucleotide polymorphism) markers, and infers haplotypes for them. It does this by seeing whether it can find a set of haplotypes that resolve all diploid genotypes and that fit onto a tree without requiring any extra changes of nucleotides (in other words, they are all compatible with the same tree). The result is not only the haplotype resolution but the resulting tree, if any. The method is described in a paper: Gusfield, D., 2002 Haplotyping as perfect phylogeny: conceptual framework and efficient solutions, pp. 165-175 in Proceedings of RECOMB 2002, edited by G. Myers, S. Hannenhalli, D. Sankoff, S. Istrail, P. Pevzner et al. ACM Press, New York. The program is available as C++ and Perl source code, and as executables for Windows, for SUN SPARC Solaris, for Intel/AMD-compatible Linux, and for Mac OS X from its web site at http://wwwcsif.cs.ucdavis.edu/~gusfield/pph.html.

Marc Suchard and Vladimir Minin of the Department of Biomathematics at the University of California, Los Angeles (msuchard (at) ucla.edu) have released DualBrothers version 1.1 , recombination detection software based on the dual Multiple Change-Point (MCP) model. . The model allows for changes in topology and evolutionary rates across sites in a multiple sequence alignment. It uses a Bayesian approach together with an MCMC (Markov chain Monte Carlo) sampling to simulate from the posterior distribution of the dual MCP model parameters. It is described in the papers:

• Minin, V. N., K. S. Dorman, and M. A. Suchard. 2005. Dual multiple change-point model leads to more accurate recombination detection, Bioinformatics 21: 3034-3042.
• Suchard M. A., R. E. Weiss, K. S. Dorman. and J. S. Sinsheimer. 2003. Inferring spatial phylogenetic variation along nucleotide sequences: a multiple change-point model. Journal of the American Statistical Association 98: 427-437.
• Suchard M. A., R. E. Weiss, K. S. Dorman, and J. S. Sinsheimer. 2002. Oh brother, where art thou? a Bayes factor test for recombination with uncertain heritage. Systematic Biology 51: 715-728.

Karin Dorman of the Department of Genetics, Development and Cell Biology of Iowa State University, Ames, Iowa (kdorman (at) iastate.edu) has written cBrother, a C version of the DualBrothers program, with extensions. cBrother is a C version of the Java code of DualBrothers, developed by Suchard et al. as a Bayesian multiple change point model to test for the presence of rare recombination events in the history of a set of sampled sequences. It is available as C source code. It can be downloaded from its web site at http://rumi.gdcb.iastate.edu/software/index.xml

Simone Linz, Achim Radtke, and Arndt von Haeseler of the Center of Integrative BioInformatics Vienna of the University of Vienna, Austria (jarndt.von.haeseler (at) univie.ac.at   and  linz (at) cs.uni-duesseldorf.de) have written HGT (Horizontal Gene Transfer), a program to test for the presence of horizontal gene transfer. HGT considers the distribution of trees obtained from a set of different genes, and then simulates the trees obtained with a single species tree and different rates of horizontal gene transfer. The estimation of the rate of horizontal gene transfer is made based on the extent of differences among individual gene trees in the simulation and in the observed set of loci. The methods are described in the paper: Linz, S., A. Radtke, and A. von Haeseler. 2007. A Likelihood framework to measure horizontal gene transfer. Molecular Biology and Evolution 24: 1312-1319. HGT is available as C source code. It can be downloaded from its web site at http://www.cibiv.at/software/hgt/

Darren P. Martin and Ed Rybicki of the Microbiology Department of the University of Cape Town, Cape Town, South Africa Darrin.Martin (at) uct.ac.za) have released RDP3 (Recombination Detection Program), version 3.27, a program that applies a large number of recombination detection and analysis algorithms. This includes many of the methods used in other recombination-detection programs. In all it has about 12 different methods. The software runs under Windows and combines highly automated screening of large numbers of sequences with a highly interactive interface for examining the results of the analyses. It is described in the paper: Martin, D. P., and E. P. Rybicki. 2000. RDP: detection of recombination amongst aligned sequences. Bioinformatics 16: 562-563. It is available as Windows executables. It can be downloaded from its web site at http://darwin.uvigo.es/rdp/rdp.html    An older version, RDP2, is also available there, as is an "unstable" early release of RDP4.

Robert Beiko and Nicholas Hamilton of the Institute for Molecular Bioscience at the University of Queensland, Australia (beiko (at) cs.dal.ca) have released EEEP (Efficient Evaluation of Edit Paths), version 1.0, a program for inference of lateral genetic transfer by comparison of phylogenetic trees. EEEP performs subtree prune-and-regraft (SPR) operations on a rooted reference tree to reconcile it with a user-supplied tree inferred from data. The rooting of the reference tree is used to constrain the SPR operations that are allowed. The test tree need not be rooted or binary, and may contain an incomplete subset of the taxa represented in the reference tree. EEEP has been successfully compiled under RedHat Linux and AIX, as well as in Mac OS X and Windows XP. It is described in the paper: Beiko, R.G., and N. Hamilton. 2006. Phylogenetic identification of lateral genetic transfer events. BMC Evolutionary Biology 6: 15, in which it was used to infer LGT events on 16,000 genes. It is available as C++ source code, Windows executables and Linux executables. It can be downloaded from its web site at http://bioinformatics.org.au/eeep

Gary Olsen of the Department of Microbiology, University of Illinois, Urbana, Illinois (gary  (at) phylo.life.uiuc.edu) has written dnarates version 1.1.0. It reads a set of DNA sequences and a tree, and for that tree makes a maximum likelihood estimate of the rate of evolution at each site. This is done by taking the rate at each site as a separate parameter and maximizing the likelihood with respect to all those parameters. The program is available as generic C source code. It is based in part (with my permission) on code from my PHYLIP program DNAML. dnarates is available from the IUBIO phylogeny software page at http://iubio.bio.indiana.edu/soft/molbio/evolve/

Bette Korber of the Theoretical Division, Los Alamos National Laboratory , Los Alamos, New Mexico (btk  (at) t10.lanl.gov) and her colleagues have released RevDNArates which is a version of Gary Olsen's program dnarates which uses the REV (general reversible) model of DNA evolution and calculates the maximum likelihood estimate of rate of change at each site (one parameter per site). They used it for the results in the paper: B. Korber, M. Muldoon, J. Theiler, F. Gao, R. Gupta, A. Lapedes, B. H. Hahn, S. Wolinksy and T. Bhattacharya. 2000. Timing the ancestor of the HIV-1 pandemic strains. Science 288: 1789-1796. The program is available as C source code for Unix from the web site for the programs from that paper at http://www.santafe.edu/~btk/science-paper/bette.html.

Sonja Meyer and Arndt von Haeseler, then of the Insititut für Bioinformatik, Heinrich Heine Universität, Düsseldorf, Germany (von Haeseler is now at the Center for Integrative Bioinformatics Vienna, and his email address is arndt.von.haeseler (at) &nbps;univie.ac.at) have released PARAT, version 0.9.1. This program infers a phylogeny and also site-specific evolutionary rates (one for each site). It can do so for up to 100 sequences directly. Above 100 sequences, it samples sets of sequences and estimates the rates from each such set, and then averages the resulting rates. It is distributed as open source C source code, which can readily be compiled and installed. PARAT is decscribed in a paper: Meyer, S. and A. von Haeseler. 2003. Identifying site specific substitution rates. Molecular Biology and Evolution 20: 182-189. It is available at its web site at http://www.cibiv.at/software/parat/

Itay Mayrose of the Department of Cell Research and Immunology of the George S. Wise Faculty of Life Sciences, Tel Aviv University, Israel (itaymay  (at) post.tau.ac.il ) has written Rate4Site version 2.01, a program to estimate rates of evolution at different sites in protein sequences. Rate4Site uses aligned protein sequences, constructs a tree by a neighbor-joining or uses a user-defined input tree, and then infers the branch lengths and the rates of evolution at the sites. These are assumed to be drawn from a Gamma distribution and can be estimated either by maximizing the likelihood of the tree with respect to each of the rates, or by using a Bayesian inference with the Gamma distribution as the prior (the parameters of the Gamma distribution are estimated empirically so that this is an Emprical Bayes method). The methods are described in the paper: Mayrose, I., D. Graur, N. Ben-Tal and T. Pupko. 2004. Comparison of site-specific rate-inference methods: Bayesian methods are superior. Molecular Biology and Evoution 21: 1781-1791. It is available as C++ source code and Windows executables. It can be downloaded from its web site at http://www.tau.ac.il/~itaymay/cp/rate4site.html

Itay Mayrose and Tal Pupko of the Department of Cell Research and Immunology of Tel Aviv University, Tel Aviv, Israel (itaymay (at) post.tau.ac.il) have produced McRate (Markov Chain monte carlo RATE estimation), version 1.0, a program to estimate rates of evolution at different sites. McRate calculates the relative evolutionary rate at each site using a probabilistic-based evolutionary model. This allows taking into account the stochastic process underlying sequence evolution within protein families. Most importantly, McRate uses Bayesian Markov chain Monte Carlo (MCMC) methodology to integrate over the space of all possible trees. Hence, McRate does not assume a pre-existing phylogenetic tree under which the sequences relate. McRate is described as superior to methods that rely on a single tree only. Its methods and the program are described in the papers:

• Mayrose I, D. Graur, N. Ben-Tal, and T. Pupko. 2004. Comparison of site-specific rate-inference methods for protein sequences: Bayesian methods are superior. Molecular Biology and Evolution 21: 1781-1791.
• Mayrose, I., A. Mitchell, and T. Pupko. 2004. Site-specific evolutionary rate inference: taking phylogenetic uncertainty into account. Journal of Molecular Evolution 60(3): 315-326.

Jessica Leigh, Ed Susko, Manuela Bumgartner, and Andrew Roger of the Department of Biochemistry and Molecular Biology and the Department of Mathematics and Statistics of Dalhousie University, Halifax, Nova Scotia, Canada (jleigh (at) dal.ca) have written Concaterpillar version 1.2, a program that carries out a hierarchical likelihood ratio test for phylogenetic congruence. It tests for two kinds of hypotheses in supermatrix analysis. The first is the null hypothesis (H0) that the phylogenies of markers in the supermatrix are congruent. If we cannot reject congruence for a set of markers, the second hypothesis to test is whether or not the markers to be combined have significantly different evolutionary dynamics (branch lengths and rates-across-sites parameters); that is, whether they should be concatenated or subjected to separate analysis. The methods are described in the paper: Leigh, J. W., E. Susko, M. Baumgartner, Roger AJ. 2008. Assessing congruence in phylogenomic data. Systematic Biology 57: 104-115. It is available as Python script. It uses the program RAxML to infer trees, and the SciPy Python library as well. It can be downloaded from its web site at http://rogerlab.biochemistryandmolecularbiology.dal.ca/Software/Software.htm#Concaterpillar

Haichun Wang, Matthew Spencer, Ed Susko, and Andrew Roger of the Department of Mathematics and Statistics and of the Department of Biochemistry and Molecular Biology of Dalhousie University, Halifax, Nova Scotia, Canada (hcwang (at) mathstat.da.ca) have produced PROCOV (PROtein COVarion analysis), version 1.3.2, a program for maximum likelihood estimation of phylogeny under protein covarion models. PROCOV computes the likelihood of a given tree under the rates-across-sites model or under the covarion-like model of Tuffley and Steel, the model of Huelsenbeck, and the model of Galtier, as well as for a general model that combines features of both the Huelsenbeck and Galtier models. Procov can also optimize tree topologies with subtree pruning-regrafting to search tree space. Procov is very computationally slow, so this is most useful for small trees. It is described in the paper: Wang, H-C, M. Spencer, E. Susko, and A. J. Roger. 2007. Testing for covarion-like evolution in protein sequences. Molecular Biology and Evolution 24: 294-305. It is available as C source code. The authors suggest using the BLAS matrix library when compiling it. It can be downloaded from its web site at http://www.mathstat.dal.ca/~hcwang/procov.html

  Nick Goldman (goldman  (at) ebi.ac.uk) of the European Bioinformatics Institute, Hinxton, UK and his group have produced EDIBLE, a program for Experimental Design and Information By Likelihood Exploration, version 1.00. It allows the user to read in a phylogeny, explore the effect on the likelihood and on the information matrix (the second derivatives of the likelihood with respect to the parameters) and measures of overall information of changing branch lengths in the tree and moving branch lengths around. It also can carry out simulations, producing multiple data sets on the tree in question. The program is described in two papers:

• Goldman, N. 1998. Phylogenetic information and experimental design in molecular systematics. Proceedings of the Royal Society London B 265: 1779-1786
• Massingham, T. and N. Goldman. 2000. EDIBLE: experimental design and information calculations in phylogenetics. Bioinformatics 16: 294-295.

Bret Larget, of the Departments of Statistics and Botany at the University of Wisconsin, Madison (larget  (at) stat.wisc.edu) and Donald Simon of the Department of Mathematics and Computer Science, Duquesne University, Pittsburgh, Pennsylvania (simon  (at) mathcs.duq.edu) have written BAMBE (Bayesian Analysis in Molecular Biology and Evolution) version 4.01a, a program for Bayesian analysis of phylogenies with DNA sequence data. It uses a prior distribution of trees and arearrangement mechanism introduced in the paper: Mau, B., M. A. Newton, and B. Larget. 1997. Bayesian phylogenetic inference via Markov chain Monte Carlo methods. Molecular Biology and Evolution 14: 717-724. The trees and parameter values are sampled by a Metropolis algorithm Markov Chain Monte Carlo sampling. The resulting posterior distribution can be used to characterize the uncertainty about not only the tree, but the parameters of the substitution model as well. The program is in C++ source code for Unix, and is distributed from his web site at http://www.stat.wisc.edu/~larget/. A Windows executable of an earlier version is also available there. The 2.03 and earlier versions are also available at a web page at Duquesne University. BAMBE is also available as a web server at the Institut Pasteur in Paris.

Mark Pagel and Andrew Meade of the School of Biological Sciences of the University of Reading, Reading, U.K. (m.pagel (at) reading.ac.uk) have written BayesPhylogenies, version 1.1, a program for estimating phylogenies by Bayesian inference. BayesPhylogenies uses Bayesian Markov Chain Monte Carlo (MCMC) or Metropolis-coupled Markov chain Monte Carlo (MCMCMC) methods. The program allows a range of models of gene sequence evolution, models for morphological traits, models for rooted trees, gamma and beta distributed rate-heterogeneity, and implements a mixture model that allows the user to fit more than one model of sequence evolution without partitioning the data. It is described in the paper: Pagel, M. and Meade, A. 2004. A phylogenetic mixture model for detecting pattern-heterogeneity in gene sequence or character-state data. Systematic Biology 53: 571-581. It is available as Windows executables, Linux executables, and Powermac Mac OS X executables. It can be downloaded from its web site at http://www.evolution.rdg.ac.uk/BayesPhy.html

Nicolas Lartillot of the LIRMM (Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier) of the Université de Montpellier II, Montpellier, France (nicolas.lartillot (at) lirmm.fr) has written PhyloBayes version 2.1c, a Bayesian phylogeny package for protein sequences using a mixture model. PhyloBayes is a Bayesian Monte Carlo Markov Chain (MCMC) sampler for phylogenetic reconstruction using protein alignments. Compared to other phylogenetic MCMC samplers, the main distinguishing feature of PhyloBayes is the underlying probabilistic model, CAT. This is a mixture model especially devised to account for site-specific features of protein evolution. It is particularly well suited for large multigene alignments. PhyloBayes can also do divergence time estimation with a relaxed molecular clock, posterior predictive analyses, including a compositional homogeneity test, and data recoding (analogous to R/Y coding, but for amino-acids). The CAT model is described in the paper: Lartillot, N. and H. Phillipe. 2004. A Bayesian mixture model for across-site heterogeneities in the amino-acid replacement process. Molecular Biology and Evolution 21(6): 1095-1109. PhyloBayes is a package of programs that operate together to do the steps of the analysis. It is distributed as C++ source code and Linux executables. The C++ source code can be compiled on Linux, Windows, or Mac OS X systems. It can be downloaded from its web site at http://www.atgc-montpellier.fr/phylobayes/binaries.php A server is here

  John Huelsenbeck (johnh  (at) berkeley.edu) of the the Department of Integrative Biology of the University of California, Berkeley, and Fredrik Ronquist (Fredrik.Ronquist  (at) nrm.se) of the Naturhistoriska riksmuseet, Stockholm, Sweden have written MrBayes, version 3.1.2, a program for Bayesian inference of phylogenies from nucleic acid sequences, protein sequences, and morphological characters. It assumes a prior distribution of tree topologies and uses Markov Chain Monte Carlo (MCMC) methods to search tree space and infer the posterior distribution of topologies. It reads sequence data in the NEXUS file format, and outputs posterior distribution estimates of trees and parameters. It can also use a hierarchical Bayesian framework to infer sites that are under natural selection. It allows for rate variation among sites and a variety of models of sequence evolution. MrBayes is available as a Macintosh (PowerMac) executable, a Windows executable, or as source code in C. It allows for multiple-chain Metropolis-coupled Markov Chain Monte Carlo (MC³) runs for more extensive search, and can be asked to spread jobs over a cluster of computers using the MPI message-passing interface. (Incidentally, since Bayes was Reverend Bayes, shouldn't it be named RevBayes?). MrBayes executables, source code, and documentation are available from the MrBayes web page at http://mrbayes.net.

Torsten Eriksson of the Bergius Botanical Garden, Stockholm, Sweden (torsten  (at) bergianska.se) makes available MrBayes tree scanners. These are two Perl scripts that scan the output parameter files produced by MrBayes. One saves the tree corresponding to the best sample. The other saves all trees that contain a specific node (a specific grouping). They are distributed together, and available from his software distribution site at http://www.bergianska.se/index_forskning_soft.html.

Marc Suchard of the Department of Biomathematics of the David Geffen School of Medicine at UCLA, Los Angeles (msuchard (at) ucla.edu) has written MrBayesPlugin, a Java plugin module enabling Geneious to run MrBayes. With it, Geneious v2.5.4 (or above) is enabled perform and analyze simple Bayesian phylogenetic reconstruction using MrBayes. It is available as Java executables. It can be downloaded from its web site at http://www.biomath.ucla.edu/msuchard/software/software.htm

  Alexei Drummond, of the Department of Computer Science of the University of Auckland, New Zealand (alexei (at) cs.auckland.ac.nz) and Andrew Rambaut (a.rambaut (at) ed.ac.uk)), of the Institute for Evolutionary Biology, University of Edinburgh, Scotland, and formerly of the Department of Zoology, University of Oxford, Oxford, U.K., have developed BEAST (Bayesian Evolutionary Analysis Sampling Trees), version 1.4.1. This is a general Bayesian inference program for parameters of evolutionary models when the trees are coalescent trees. A variety of nucleotide substitution models including relaxed molecular clocks are allowed, and population models that include exponential population growth and divergence time between populations are included. Most of the analyses use Bayesian sampling to infer parameters by averaging over the posterior on the trees. For the purposes of this listing, the two relevant features are the ability to output a sample of the trees, so that the program can be used for Bayesian tree inference in clocklike models, and the ability to infer the divergence time between populations. The general approach used by BEAST is described in the paper: Drummond, A. J., G. K. Nicholls, A. G. Rodrigo, and W. Solomon. 2002. Estimating mutation parameters, population history and genealogy simultaneously from temporally spaced sequence data. Genetics 161: 1307-1320. BEAST is available as a Java executable which will run on any system with Java 1.4 or later. There are specific packages available for Mac OS X and for Windows as well as the general distribution. These are all distributed from its web site at http://beast.bio.ed.ac.uk/Main_Page

 Alexei Drummond, of the Department of Computer Science of the University of Auckland, New Zealand (alexei (at) cs.auckland.ac.nz) and Andrew Rambaut (a.rambaut (at) ed.ac.uk)), of the Institute of Evolutionary Biology at the University of Edinburgh, Scotland, U.K. have released Tracer, version 1.2. This is a program for analyzing the results of Bayesian sampling runs using either BEAST or MrBayes. It allows analysis of the progress of sampling the parameters. For the purposes of this listing, the relevant feature is an ability to use the trees sampled by these programs to do a Bayesian skyline plot analysis of birth and death rates of lineages. Tracer is available as a Java executable from its web site at http://tree.bio.ed.ac.uk/software/tracer/ with specific packages for Mac OS X and Windows as well.

Johan Nylander of the Department of Botany of the University of Stockholm, Stockholm, Sweden (johan.nylander (at) abc[dot]se) has released burntrees version 0.1.7, a script for manipulating the output from MCMC programs (MrBayes, BEAST). It is a script for manipulating tree (*.t, *.trprobs, *.con) and parameter (*.p) files from MrBayes (v.3), and other MCMC programs. The script can extract any contiguous interval of trees, or make a random selection of a fraction of them. It can also thin the chain by sampling every nth iteration. Branch lengths can also be removed from trees when they are sampled. Trees can also be converted from Nexus to Phylip (Newick) format or to altnexus format (sequence labels instead of numbers). In a similar fashion, lines can also be extracted from a MrBayes *.p file. The script comes with a helper script, catmb.pl, that concatenates files from several runs It is available as Perl script. It can be downloaded from its web site at http://www.abc.se/~nylander

Dan Rabosky of the Department of Ecology and Evolutionary Biology of Cornell University, Ithaca, New York (DLR32 (at) cornell.edu) has written laser (Likelihood Analysis of Speciation and Extinction Rates), version 2.1, an R package for a variety of analyses of changes in speciation and extinction rates. laser implements maximum likelihood methods based on the birth-death process to test whether diversification rates have changed over time and whether rates vary among lineages. The methods are described in the papers:

• Rabosky, D. L. 2006. Likelihood methods for inferring temporal shifts in diversification rates. Evolution 60: 1152-1164.
• Rabosky, D. L., S. C. Donnellan, A. L. Talaba, and I. J. Lovette. 2007. Exceptional among-lineage variation in diversification rates during the radiation of Australia's largest vertebrate clade. Proceedings of the Royal Society of London, Series B 274: 2915-2923.

Pavel Morozov and Andrey Rzhetsky of the Department of Biomedical Informatics and the Columbia Genome Center of Columbia University, New York, New York (pm259 (at) columbia.edu and andrey.rzhetsky (at) dbmi.columbia.edu) have released PHYLLAB version 1.1, A toolbox for sequence manipulation and phylogenetic analysis in MatLab. PHYLLAB takes as input a set of aligned nucleotide or amino-acid sequences, and performs phylogeny inference. Beside traditional phylogenetic methods it uses a Markov chain Monte Carlo method, evaluating the posterior distribution over tree topologies and a variety of model parameters, including parameters of substitution-rate variation under a wavelet model. The graphical interface helps users to manage input data and to visualize the most likely trees; they can also view substitution-rate plots that show the maximum posterior density (confidence) intervals. It is written in the MatLab language, and interested users can extend it easily. The PHYLLAB toolbox is continually expanding, and the authors expect to offer many more functions and scripts for different purposes soon. It is available as a MATLAB package. It can be downloaded from its web site at http://amdec-bioinfo.cu-genome.org/html/misc/Pavel/phyllab.html

Peter Foster (p.foster  (at) nhm.ac.uk) of the Natural History Museum, London, England has released p4 version 0.81, a Python package for maximum likelihood and Bayesian phylogenetic analyses of molecular sequences. This is not a program with menus and buttons; it is invoked using the Python language, which the user should know before attempting to use it. It can do Bayesian inference of phylogenies, as well as computation of likelihoods of trees. It also has facilties for viewing large trees and for manipulation of trees. It needs Python 2.3 or better and the Gnu Scientific Library (GSL) installed on the machine. It is distributed as Python source code at its web site at http://www.bmnh.org/web_users/pf/p4.html

Mike Charleston (mcharles  (at) it.usyd.edu.au) of the Sydney University Biological Informatics and Technology Centre, Sydney, Australia has developed Spectrum, a program for finding bipartition spectra from phylogenetic molecular and distance data, according to the method of Hendy et al. (1994) (Hadamard transforms) for moderately sized data sets (up to 18 taxa). The program also implements a branch-and-bound search for the "closest tree" - that is, the tree whose expected spectrum is closest to the spectrum derived from the observed data. Mac OS PowerMac, 68k Mac OS, and Windows executables are available from his software web site at http://www.it.usyd.edu.au/~mcharles/.

Ingrid Jakobsen, Susan Wilson, and Simon Easteal, of Australian National University, Canberra, released partimatrix. (Ingrid Jakobsen is currently at the Department of Mathematics of the University of Queensland, Australia, i.jakobsen  (at) uq.edu.au). This program computes a "partition matrix" from aligned DNA sequence data. The method finds partitions of the sequences into two groups and presents a matrix which describes the conflict and agreement among these partitions. The objective is to discover parts of the DNA sequence which imply different trees. It is described in the paper by I. B. Jakobsen, S. R. Wilson and S. Easteal. 1997. The Partition Matrix: Exploring variable phylogenetic signals along nucleotide sequence alignments. Molecular Biology and Evolution 14: 474-484. The program is distributed as C source code for Unix systems with X Windows. It seems not to be available from Dr. Jakobsen, but is ` available from a site at the Centro Nacional de Cálculo Científico de la Universidad de Los Andes, Venezuela at http://www.cecalc.ula.ve/BIOINFO/servicios/herr1/PARTIMATRIX/manual.htm

Carla Cummins and James McInerney of the Department of Biology of the National University of Ireland Maynooth (james.o.mcinerney (at) nuim.ie) has released TIGER version 1.02, A program for identifying rapidly-evolving characters in a matrix of evolutionary characters. TIGER is open source software for identifying rapidly evolving sites (columns in an alignment, or characters in a morphological dataset). It can deal with many kinds of data (molecular, morphological etc.). Sites like these are often removed or reweighted in order to improve phylogenetic reconstruction, as they might not hold much phylogenetic information and therefore might simply be a source of noise. It is described in the paper: Cummins, C. A. and J. O. McInerney. 2011. A method for inferring the rate of evolution of homologous characters that can potentially improve phylogenetic inference, resolve deep divergence and correct systematic biases. Systematic Biology 60 (6): 833-844. doi: 10.1093/sysbio/syr064. It is available as Python script and Mac OS X universal executables. It can be downloaded from its web site at http://bioinf.nuim.ie/tiger

Yasuo Ina of the National Institute of Agrobiological Resources, Tsukuba, Japan developed ODEN version, a package of programs for doing distance matrix analyses on nucleotide or protein sequences. It is described in a paper: Ina, Y. 1994. ODEN: a program package for molecular evolutionary analysis and database search of DNA and amino acid sequences. Computer Applications in the Biosciences (CABIOS) 10: 11-12. It is available free by anonymous ftp from directory pub/unix/oden on ftp.dna.affrc.go.jp as C source code for Unix systems.

Angela Lüttke and Rainer Fuchs (then of the European Molecular Biology Laboratory; Fuchs is currently at Biogen, Inc., Cambridge, Massachusetts) wrote MacT, a package of programs for Mac OS Macintoshes that compute distances and compute Neighbor-Joining phylogenies for them. The programs work on 4 through 26 sequences, and source code in Microsoft QuickBasic is provided as well as compiled executables. The package is free and is available on the molecular biology software servers. For example, it is available at the Indiana University IUBIO server at http://iubio.bio.indiana.edu/soft/molbio/mac/. It is described in a paper: Luttke, A. and R. Fuchs. 1992. MacT: Apple Macintosh programs for constructing phylogenetic trees. Computer Applications in the Biosciences 8: 591-594.

Nicholas Galtier of the University of Lyon (galtier  (at) biomserv.univ-lyon1.fr) has written Phylo_win, a "graphic interface" for molecular phylogenetic inference. It performs neighbor-joining, parsimony and maximum likelihood methods and can bootstrap with any of them. Many distances can be used including Jukes and Cantor, Kimura, Tajima and Nei, Galtier and Gouy (1995), LogDet for nucleotidic sequences, Poisson correction for protein sequences, Ka and Ks for codon sequences. Species and sites to include in the analysis are selected by mouse. Reconstructed trees can be drawn, edited, printed, stored, evaluated according to numerous criteria. Taxonomic species groups and sets of conserved regions can be defined by mouse in both tools and stored into sequence files, thus avoiding multiple data files. It is entirely mouse-driven. Most usual sequence file formats are read: CLUSTAL, FASTA, PHYLIP, MASE. It runs under X windows on many Unix workstations. It is described in the paper: Galtier, N., M. Gouy, and C. Gautier. 1996. SeaView and Phylo_win, two graphic tools for sequence alignment and molecular phylogeny. Computer Applications in the Biosciences 12: 543-548. Phylo_win is now considered by Galtier to have been superseded by his program SeaView. Phylo_win is distributed as C source code (to compile it one needs the NCBI Vibrant tool kit). It is also available as executables for SunOS, Solaris, SGI Unix, IBM RISC Unix, Linux, HP/UX, and DEC Alpha (Digital Unix). It can be fetched from its web page at http://pbil.univ-lyon1.fr/software/phylowin_legacy.html. It can also be obtained by anonymous ftp from biom3.univ-lyon1.fr in directory pub/mol_phylogeny. A Digital OpenVMS executable is also available as http://www.tmk.com/ftp/vms-freeware/mathog/.

Heiko Schmidt, of the Center for Integrative Bioinformatics of the University of Vienna (heiko.schmidt (at) univie.ac.at), Korbinian Strimmer, now at the Department of Statistics of the University of Münich, Germany (korbinian.strimmer (at) lmu.de), and Arndt von Haeseler, now at the Center for Integrative Bioinformatics Vienna (arndt.von.haeseler (at) &nbps;univie.ac.at) have developed TREE-PUZZLE version 5.2, (formerly called PUZZLE) a program for maximum likelihood analysis for nucleotide and amino acid alignments. TREE-PUZZLE infers phylogenies by "quartet puzzling", a method that applies maximum likelihood tree reconstruction to all possible quartets of taxa and subsequently tries to combine most of the four-taxa maximum likelihood trees to construct an overall maximum likelihood tree. Usually there are several possible solutions. A consensus tree generated from the quartet puzzling trees shows nodes that are well supported. More details about the algorithm and on the phylogenetic accuracy can be found in the papers:

• Strimmer, K. and A. von Haeseler. 1996. Quartet puzzling: A quartet maximum likelihood method for reconstructing tree topologies. Molecular Biology and Evolution 13: 964-969.
• Strimmer, K., and A. von Haeseler. 1997. Likelihood-mapping: A simple method to visualize phylogenetic content of a sequence alignment. Proceedings of the National Academy of Sciences (USA) 94: 6815-6819.
• Schmidt, H.A., K. Strimmer, M. Vingron, and A. von Haeseler. 2002. TREE-PUZZLE: maximum likelihood phylogenetic analysis using quartets and parallel computing. Bioinformatics 18: 502-504.

   Mike Holder, formerly of the High Performance Computing Center of the University of Houston and Andrew Roger (aroger (at) is.dal.ca) of the Department of Biochemistry and Molecular Biology of Dalhousie University, Halifax, Canada have produced a shell script program for Unix systems, puzzleboot, version 1.03, that allows the analysis of multiple bootstrapped data sets with TREE-PUZZLE. It is designed for use with the distance matrix option of TREE-PUZZLE, to make use of the distance calculation methods. It is available from the Roger lab software page at http://rogerlab.biochemistryandmolecularbiology.dal.ca/Software/Software.htm#puzzleboot

• SplitsTree4, a Java version which can run under Linux, Windows, and Mac OS X.
• SplitsTree 3.2, which is available as a Windows executable, a Linux, and a Solaris executable, and also a Mac OS X version by Rod Page
• SplitsTree 3.1, also as a Windows and a Linux version
• SplitsTree 2.4, for Mac OS.

Igor Kuznetsov and Pavel Morozov, then of the Institute of Cytology and Genetics, Novosibirsk, Russia produced GEOMETRY, a package for nucleotide sequence analysis using the method of statistical geometry in sequence space. Kuznetsov (ikuznetsov (at) albany.edu) is currently at the Department of Epidemiology and Biostatistics at the State University of New York in Albany, Morozov (pm259 (at) columbia.edu) is currently at the Irving Cancer Research Center at Columbia University. The method is described in this paper: Eigen, M., R. Winkler-Oswatitsch, and A. Dress. 1988. Statistical geometry in sequence space: A method of quantitative comparative sequence analysis, Proc. Natl. Acad. Sci. USA 85: 5913-5917. The program is described in the article: Kuznetsov, I. and P. Morozov. 1996. GEOMETRY: a software package for nucleotide sequence analysis using statistical geometry in sequence space. Computer Applications in the Biosciences (CABIOS) 12: 297-301. The package uses the same data formats for sequence and tree input as the ones used in the VOSTORG package. GEOMETRY is available as a DOS executable. It is available for downloading by ftp from the EMBL file server ftp.ebi.ac.uk in directory pub/software/dos as file geom.zip.

  Vincent Berry of the LIRMM, Université de Montpellier, France (vberry  (at) lirmm.fr) has released PhyloQuart version 1.4, a package of programs inferring phylogenies from quartets. It is able to use either nucleotide sequences or distances. It implements the Q* method of tree reconstruction, which is inspired by the work of Bandelt and Dress, and is described in the paper: Berry, V. and O. Gascuel. 2000. Inferring evolutionary trees with strong combinatorial evidence. Theoretical Computer Science 240: 271-298. PhyloQuart is available as C source code which can be compiled on Unix systems, from its web site at http://www.lirmm.fr/~vberry/PHYLOQUART/phyloquart.html.

Le Sy Vinh, now of the Computer Science Department, University of Engineering and Technology, Vietnam National University Hanoi (vinhbio (at) gmail.com), and Arndt von Haeseler, now of the Center for Integrative Bioinformatics Vienna (arndt.von.haeseler (at)  univie.ac.at) have released IQPNNI version 3.3.2 (Important Quartet Puzzling and NNI Operation). This program uses selected quartets called Important Quartets of species to build a preliminary tree, rearrange it using the maximum likelihood criterion by nearest-neighbor interchanges, and then use further examination of quartets to remove and reposition some of the species. It is described in some papers:

• Vinh, L. S. and A. von Haeseler. 2004. IQPNNI: Moving fast through tree space and stopping in time. Molecular Biology and Evolution 21: 1565-1571.
• Bui Quang Minh,, B. Q. L. S. Vinh, A von Haeseler and H. A. Schmidt. 2005. pIQPNNI: Parallel reconstruction of large maximum likelihood phylogenies. Bioinformatics 21(19): 3794-3796.
• Minh, B. Q., L. S. Vinh, H. A. Schmidt, and A. von Haeseler. 2006. Large maximum likelihood trees. Proceedings of the NIC Symposium 2006 pp. 357-365, Forschungszentrum Jülich, Germany.

Stephen J. Willson (swillson  (at) iastate.edu) of the Department of Mathematics, Iowa State University, has produced a package of programs to infer phylogenies from quartets of species. They infer phylogenies of individual quartets by parsimony, and in combining them use information on how strongly the phylogeny for that quartet is preferred over its alternatives, or by measures of how well the group fits into a given placement on a tree, as judged by quartets. The methods are described in two papers:

• Willson, S. J. 1998. Measuring inconsistency in phylogenetic trees, Journal of Theoretical Biology 190: 15-36
• Willson, S. J. 1998. Building phylogenetic trees from quartets by using local inconsistency measures . Molecular Biology and Evolution 16: 685-693.

James Lake of the Department of Molecular, Cell and Developmental Biology of the University of California, Los Angeles (lake  (at) mbi.ucla.edu) has released Gambit, which implements a method called Boostrapper's Gambit. The method involves bootstrap sampling sequences, computing trees for quartets of species, and assembling larger trees out of quartets that have significant boostrap support. One of the methods available to estimate trees from the quartets is paralinear (LogDet) distances. Other distance methods and parsimony are also available. The Bootstrapper's Gambit method is described in a paper: Lake, J. A. 1995. Calculating the probability of multitaxation evolutionary trees: Bootstrappers gambit. Proceedings of the National Academy of Sciences, USA 92: 9662-9666. The program is available as a DOS executable, free as a beta release to noncommercial users on a trial basis until January 1, 2003. (It is unclear from the web site whether a free version is to be available to noncommercial users after that point -- a previous deadline was extended). Commercial users are asked to pay $50 on a shareware basis. The program is available at its web site at http://genomics.ucla.edu/gambit/.

  Arne Röhl, Peter Forster, and Hans-Jürgen Bandelt (Forster has more recently been Senior Lecturer Forensic Science in the Faculty of Science and Technology of Anglia Ruskin University, Cambridge, U.K.), e-mail address pf223  (at) cam.ac.uk, and Bandelt is at the Fachbereich Mathematik, University of Hamburg, Bundesstrasse 55, 20146 Hamburg, Germany, e-mail address bandelt  (at) math.uni-hamburg.de) have written Network version 4.516, a program to infer networks (which have more connections than trees) from non-recombining DNA, STR, amino acid, and RFLP data. The networks are either reduced median networks or median-joining networks, method which are described in the papers:

• Bandelt H.-J., P. Forster, B. C. Sykes, and M. B. Richards. 1995. Mitochondrial portraits of human populations using median networks. Genetics 141: 743-53.
• Bandelt, H-J., P. Forster, and A. Röhl. 1999. Median-joining networks for inferring intraspecific phylogenies. Molecular Biology and Evolution 16: 37-48.

  Mike Hendy, Katharina T. Huber, Michael Langton, Vincent Moulton, and David Penny have written Spectronet version 1.27, a program that computes a collection of weighted splits or partitions and allows the user to interactively analyze the results with a series of tools. Hendy and Penny are at Massey University, New Zealand (m.hendy (at) massey.ac.nz and d.penny  (at) massey.ac.nz), Huber and Moulton are at the School of Computational Science of the University of East Anglia, U.K. (Katharina.Huber  (at) cmp.uea.ac.uk and Vincent.Moulton (at) cmp.uea.ac.uk). Spectronet can read molecular sequence or discrete character data, compute splits by Hadamard conjugation or directly, compute and display compatibility matrices of characters, make reduced median networks, and plot networks by making a Lentoplot. Spectronet is described in a paper: Huber, K. T., M. Langton, D. Penny, V. Moulton and M. Hendy. 2002. Spectronet: A package for computing spectra and median networks. Applied Bioinformatics 1: 159-161. It is available as a Windows executable from its web site at http://awcmee.massey.ac.nz/spectronet/index.html.

Steven Kelk, Leo van Iersel, Judith Keijsper, and Leen Stougie of the Centrum voor Wiskunde en Informatica (CWI) and Technische Universiteit Eindhoven (TU/e), Netherlands (S.M.Kelk (at) cwi.nl) have produced LEVEL2 version 0.91, which constructs level-2 phylogenetic networks from dense sets of rooted triplets. This program takes as input a dense set of rooted triplets and attempts to construct a level-2 phylogenetic network from them (or level-1, or level-0, if level-2 is not necessary). Triplets are the rooted analogue of quartets, and a dense set of triplets is one where for every subset of three taxa there is at least one triplet. A level-k phylogenetic network is a rooted phylogenetic network where every biconnected component in the underlying, undirected graph contains at most k recombination vertices. The program produces an image of the resulting network, if it is found. It is described in the paper: van Iersel, L., J. Keijsper, S. Kelk, and L. Stougie. 2007. Constructing level-2 phylogenetic networks from triplets. arXiv:0707.2890v1 [q-bio.PE]. It is available as Java source code, and also requires that the DOT graph description package be installed. It can be downloaded from its web site at Sourceforge at http://sourceforge.net/projects/level2/ and a general web page about it is at its web site at http://homepages.cwi.nl/~kelk/level2triplets.html

Luay Nakhleh, Derek Ruths, and Cuong Than of the Department of Computer Science of the Rice University, Houston, Texas (nakhleh (at) cs.rice.edu) have released PhyloNet (Phylogenetic Network analysis ), version 2.3, a phylogeny package with tools for reconstructing and analyzing phylogenetic networks. It has programs for inferring horizontal gene transfer events, by estimating the SPR distance between two trees (along with a bootstrap-based measure of support), and interspecific recombination, by using maximum parsimony. It also has tools for enumerating the trees and clusters of taxa within a given network, comparing the topologies of networks, estimating the strain tree of bacterial genomes from multi-locus data, and enumerating valid coalescent histories of a gene tree within the branches of a species tree. It is described in the paper: Than, C., D. Ruths, and L. Nakhleh, 2008. PhyloNet: A Software Package for Analyzing and Reconstructing Reticulate Evolutionary Relationships. Under Review. It is available as Java executables. It can be downloaded from its web site at http://bioinfo.cs.rice.edu/phylonet/index.html

Guohua Jin and Luay Nakhleh of the Department of Computer Science of Rice University, Houston, Texas (jin (at) cs.rice.edu and nakhleh (at) cs.rice.edu) have produced NEPAL (NEtwork Parsimony And Likelihood), version 1.1, a suite of tools for reconstructing and analyzing reticulate (non-treelike) evolutionary relationships using the maximum parsimony and maximum likelihood criteria. It is used to identify horizontal gene (or partial gene) transfers between species. NEPAL reads in a species tree in Newick format or a network from NEPAL or RIATA-HGT output, and sequence data. It returns the maximum parsimony or maximum likelihood score of the input or generated trees or networks. The user can control the number of additional edges added to the input tree. The methods are described in the papers:

• Jin, G., L. Nakhleh, S. Snir, and T. Tuller. 2006. Maximum likelihood of phylogenetic networks. Bioinformatics 22(21): 2604-2611.
• Jin, G., L. Nakhleh, S. Snir, and T. Tuller. 2007. Efficient parsimony-based methods for phylogenetic network reconstruction. Bioinformatics 23: e123-e128.

   Liang Liu of the Department of Agriculture and Natural Resources of Delaware State University (lliu (at) desu.edu), together with Dennis Pearl of the Department of Statistics at Ohio State University and Scott Edwards of the Department of Organismic and Evolutionary Biology at Harvard University, has released BEST (Bayesian Estimation of Species Trees), version 2.2, a phylogeny package for estimating species trees from multilocus DNA sequence data. BEST finds the joint posterior distribution of coalescent gene trees and the species tree for multi-locus data under a hierarchical Bayesian model. Proposal gene trees are made using a gene tree MCMC procedure chosen by the user in MrBayes This vector of gene trees is then paired with a species tree chosen under the constraint that the gene trees be consistent with the species tree. An MCMC importance samplier is then used to sample the species trees. It is described in the papers:

• Liu, L. and D. K. Pearl. 2007. Species trees from gene trees: reconstructing Bayesian posterior distributions of a species phylogeny using estimated gene tree distributions. Systematic Biology 56: 504-514.
• Edwards, S. V., L. Liu, and D. K. Pearl. 2007. High resolution trees without concatenation. Proceedings of the National Academy of Sciences 104: 5936-5941.
• Liu, L., D. K. Pearl, R. T. Brumfield, and S. V. Edwards. 2008. Estimating species trees using multiple-allele DNA sequence data. Evolution 62: 2080-2091.

    Ruchi Chaudhary, Mukul S. Bansal, André Wehe, David Fernández-Baca, and Oliver Eulenstein of the Department of Computer Science at Iowa State University, Ames, IA (oeulenst (at) cs.iastate.edu) have released iGTP version 1.0, a software package for large-scale phylogenetic analyses using gene tree parsimony. iGTP implements algorithms for inferring species supertrees that best reconcile the input gene trees under the gene-duplication, gene-duplication and loss, and deep coalescence cost models. iGTP extends the functionality and performance of existing gene tree parsimony software and features building effective initial trees using greedy stepwise leaf addition and the ability to have unrooted gene trees in the input. Moreover, iGTP provides a user-friendly graphical interface with integrated tree visualization software to facilitate analysis of the results. It is described in the paper: Chaudhary, R., M. S. Bansal, A. Wehe, D. Fernández-Baca and O. Eulenstein. 2010. iGTP: A software package for large-scale gene tree parsimony analysis.BMC Bioinformatics 11: 574. It is available as Windows executables, Linux executables and Mac OS X universal executables. The authors can be contacted for the source code. The executables can be downloaded from its web site at http://genome.cs.iastate.edu/CBL/iGTP/

   Andrew Roger, of the Department of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada (aroger (at) is.dal.ca) has written ELW (Expected Likelihood Weights), two PERL scripts -- elw.pl and calcwts.pl -- that, together with PAUP* and the PHYLIP program Seqboot can be used to implement the "expected likelihood weights" method of Strimmer and Rambaut, described in the paper by Strimmer, K. and A. Rambaut. 2002. Inferring confidence sets of possibly misspecified gene trees. Proceedings of the Royal Society of London Series B 269: 137-142. It calculates a confidence interval for the maximum likelihood tree using the variation of the likelihoods among bootstrap estimates of the tree. ELW can be downloaded from its entry on Roger's software web page at http://rogerlab.biochemistryandmolecularbiology.dal.ca/Software/Software.htm#elw

Naoko Takezaki of the Life Science Research Center of Kagawa University, Japan (takezaki (at) med.kagawa-u.ac.jp) wrote Lintre (Phylogenetic tests of the molecular clock and linearized tree), a package of programs for Sun workstations. The programs include:

• njboot -- construct a neighbor-joining (NJ) tree
• postree -- create a postscript file of trees
• tpcv -- conduct the two-cluster test
• branch -- conduct the branch length test
• branbst -- conduct the branch length test by bootstrap

Andrew Rambaut (a.rambaut (at) ed.ac.uk)), of the Institute for Evolutionary Biology, University of Edinburgh, Scotland, and formerly of the Department of Zoology, University of Oxford, has written TipDate version 1.2. TipDate is an application for estimating the rate molecular evolution (and hence a time-scale) for a phylogeny consisting of dated tips. These will most frequently be from viruses or other fast-evolving pathogens that have been isolated over a range of dates. The program can also return the likelihood for the simple molecular clock model (i.e., assuming that all sequences are contemporary), for a model in which rates of change at different times are drawn from a distribution, or the non-clock model. These are useful for likelihood ratio tests of the fit of the model to the data. TipDate is described in a paper: Rambaut, A. 2000. Estimating the rate of molecular evolution: incorporating non-contemporaneous sequences into maximum likelihood phylogenies. Bioinformatics 16: 395-399. TipDate is available as Mac OS executables and as source code for Linux or Unix from the IUBIO software site at http://microbe.bio.indiana.edu:7131/soft/iubionew/molbio/evolution/evolve/TipDate/. It is also available in a web-based server version from the Pasteur Institute server.

   Thomas Wilcox, formerly of the Center for Computational Biology and Informatics of the University of Texas, and more recently of Long Key Tropical Research Center, Florida (tpwilcox (at) lktrc.org) has produced Cadence version 1.0.1, a program for Bayesian relative rate tests. It is described in the paper: Wilcox, T. P., F. J.García de Leon, D. A. Hendrickson, and D. M. Hillis. 2004. Convergence among cave catfishes: Long-branch attraction and a Bayesian relative rates test. Molecular Phylogenetics and Evolution 31: 1101-1113. It is available as Powermac Mac OS X executables. It can be downloaded from its web site at the University of Texas at http://www.zo.utexas.edu/faculty/antisense/DownloadComputerPrograms.html

Jotun Hein, of the Department of Statistics, University of Oxford (hein  (at) stats.ox.ac.uk) produced TreeAlign, a multiple sequence alignment program that builds trees as it aligns DNA or protein sequences. It uses a combination of distance matrix and approximate parsimony methods, inspired by the 1973 approach of David Sankoff. It is described in two papers:

• Hein, J. J. 1990. A unified approach to phylogenies and alignments. Methods in Enzymology 183: 625-644.
• Hein, J. J. 1994. TreeAlign. pp. 349-364 in Computer Analysis of Sequence Data. edited by A. M. Grffin and H. G. Griffin. Humana Press, Tolowa, New Jersey.

  A widely-used multisequence alignment program that estimates trees as it aligns multiple sequences is ClustalW. Currently it is in version 2.0.12. It is the latest incarnation of the Clustal family of tree-based alignment programs. Clustal was originally written by Des Higgins (now at the Conway Institute, University College Dublin, Ireland) (des.higgins  (at) ucd.ie), and later versions were developed by Julie Thompson (now at the Institut de Génétique, et de Biologie Moléculaire et Cellulaire at the Université de Strasbourg, France, julie  (at) igbmc.u-strasbg.fr), Toby Gibson, (Toby.Gibson  (at) embl.de), and François Jeanmougin (jeanmougin  (at) igbmc.u-strasbg.fr) and many others. Recent features include the ability to detect read different input formats (NBRF/PIR, Fasta, EMBL/Swissprot), align old alignments, produce phylogenetic trees after alignment (Neighbor Joining trees with a bootstrap option), write different alignment formats (Clustal, NBRF/PIR, GCG, PHYLIP) and the presence of a full command line interface. Clustal exists in two major variants:

1. ClustalW which has a character-mode interface, in which the user types responses to choose options from a menu.
2. ClustalX which has a graphical user interface.

• Larkin, M. A., G. Blackshields, N. P. Brown, R. Chenna, P. A. McGettigan, H. McWilliam, F. Valentin, I. M. Wallace, A. Wilm, R. Lopez, J. D. Thompson, T. J. Gibson, and D. G. Higgins. 2007. Clustal W and Clustal X version 2.0. Bioinformatics 23: 2947-2948.
• Jeanmougin, F., J. D. Thompson, T. J. Gibson, M. Gouy, and D. G. Higgins. 1998. Multiple sequence alignment with Clustal X. Trends in Biochememical Sciences 23: 403-405.
• Thompson, J. D., T. J. Gibson, F. Plewniak, F. Jeanmougin, and D. G. Higgins. 1997. The ClustalX windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Research 24: 4876-4882.
• Higgins, D. G., J. D. Thompson, and T. J. Gibson. 1996. Using CLUSTAL for multiple sequence alignments. Methods in Enzymology 266: 383-402.
• Thompson, J.D., D. G. Higgins and T. J. Gibson. 1994. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, positions-specific gap penalties and weight matrix choice. Nucleic Acids Research 22: 4673-4680.

For the older ClustalV, there exists a Macintosh Hypercard stack, ClustToTree, that can convert its tree files to Newick Standard format (used by many other programs). ClustToTree is made available by Kai-Uwe Fröhlich at the University of Graz, Austria at http://aaa-proteins.uni-graz.at/Archiv/ClustToTreecomp.html.

ClustalW is made available on web servers by the Genebee web server at the Belozersky Institute in Moscow, and at the European Bioinformatics Institute.

Cédric Notredame of the Comparative Bioinformatics Group of the Center for Genomic Regulation (CRG), Barcelona, Spain (cedric.notredame (at) europe.com), Olivier Poirot, Fabrice Armougom, and Sebastien Moretti of the Centre National de la Recherche Scientifique Marseille-Nice Génopole, France have produced T-Coffee (Tree-based Consistency Objective Function For alignmEnt Evaluation), version 8.93. This is a multiple sequence alignment program that aims to improve on ClustalW. It is of the same general approach as ClustalW, a "progressive alignment" method, but it avoids some of the problems with the "greedy" nature of the ClustalW algorithm by taking into account more information about how the sequences all align with each other. T-Coffee is described in the paper: Notredame, C., D. Higgins, and J. Heringa. 2000. T-Coffee: A novel method for multiple sequence alignments. Journal of Molecular Biology 302: 205-217. From the point of view of this listing, the relevant features of T-Coffee are that it makes a "guide tree" and can write that tree out. It also can read in a guide tree supplied by the user. Versions from 2.00 on can align both sequences and structures. T-Coffee is available as Unix source code which can easily be compiled, and as Linux, Mac OS X and Windows binaries. It is available from its web site at http://www.tcoffee.org/Projects_home_page/t_coffee_home_page.html

Ward Wheeler of the Division of Invertebrate Zoology, American Museum of Natural History, New York (wheeler  (at) amnh.org) and David Gladstein (gladstein  (at) gladstein.org) have written MALIGN, version 2.7, a parsimony-based alignment program for molecular sequences. It implements the original suggestion by Sankoff, Morel, and Cedergren (1973) that alignment and phylogenies could be done at the same time by finding that tree that minizes the total alignment score along the tree. Jotun Hein's program TreeAlign (mentioned above) is another, more approximate but possibly faster, attempt to implement the Sankoff-Morel-Cedergren suggestion. MALIGN is one of the only programs to calculate this optimality criterion exactly (Wheeler and Gladstein's other program POY is the other). MALIGN is described in a paper: Wheeler, W. C. and D. S. Gladstein. 1994. MALIGN - A multiple sequence alignment program. Journal of Heredity 85: 417-418. MALIGN is available from its download web site at the Program in Scientific Computation of the American Museum of Natural History at http://research.amnh.org/scicomp/projects/malign.php. It is available as C source code and as binaries for Linux, Windows, Sun Solaris, SGI, and HPUX. The C source code is distributed in two forms, the ordinary one and a special version for parallel computation.

MiraiBio, a Hitachi Software company DNASIS, a general-purpose DNA and protein sequence analysis system, produced by Molecular Biology Insights, Inc. of Cascade, Colorado (but sold through Hitachi). It has many functions including primer design, plasmid maps, contig assembly, alignment, database searching, and many kinds of protein plots. For our purposes what is relevant is the ability to do multiple sequence alignment by the Higgins-Sharp method of progressive sequence alignment (the one used in ClustalV), with one of the results being a UPGMA tree based on pairwise sequence alignment scores. DNASIS is available from MiraiBio as version 3.0 (called DNASIS MAX) Windows executables, including a demo version at its web site at http://www.miraibio.com/dnasis-max/dnasis-max-overview.html. Prices are not stated there -- there is Order form that can be sent to them by email. It was formerly also available from MBI, and at that time a Windows version cost $1,895 and a Mac OS X version cost $2,995 for a 1-10 user network license.

Karl Nicholas (karlnicholas  (at) hotmail.com) with help from Hugh Nicholas (nicholas  (at) psc.edu) of the National Resource for Biomedical Supercomputing (NRBSC; www.nrbsc.org) at the Pittsburgh Supercomputing Center has produced GeneDoc, version 2.6.0.2, a program for the shading and editing of multiple sequence alignments. Its reads .MSF files and Fasta Files. The alignment can be edited by changing the position of residues in the sequences. GeneDoc includes scoring functions to assist in determining whether your aligment changes are improving the score. Support for obtaining a score via sum-of-pairs or by a phylogenetic tree is included. Phylogenetic trees can be built with either the GUI interface or imported NEXUS or PHYLIP format tree descriptions. The program runs on Windows and both 16-bit and 32-bit executables are distributed. The source code is also available there. It can be downloaded from its Web site at http://www.nrbsc.org/gfx/genedoc/gddl.htm A Windows NT version for Digital Alpha processors was formerly available from Russell Malmberg at the Botany Department of the University of Georgia but is not currently in distribution.

Ward Wheeler of the Division of Invertebrate Zoology, American Museum of Natural History, New York (wheeler  (at) amnh.org), David Gladstein (gladstein  (at) gladstein.org) and Jan De Laet of the Royal Belgian Institute of Natural Sciences, Brussels (jdelaet  (at) natuurwetenschappen.be) have written POY version 4.1.2, a program that approximately implements David Sankoff's method of searching for the tree that minimizes a parsimony criterion that includes penalties for gaps, accomplishing both searching for phylogenies and alignments. POY has algorithmic improvements by Wheeler and Gladstein that speed up the algorithm. (Their program MALIGN is the only program carrying out the full Sankoff proposal). POY implements two approximate methods, Fixed States Optimization and Direct Optimization. The methods used are described in three papers:

• Varón, A., L. S. Vinh, and W. C. Wheeler. 2010. POY version 4: phylogenetic analysis using dynamic homologies. Cladistics 26: 72-85.
• Wheeler, W. C. 1999. Fixed character States and the optimization of molecular sequence data. Cladistics 15: 379-385.
• Wheeler, W. 1996. Optimization alignment: the end of multiple sequence alignment in phylogenetics? Cladistics 12:1-9.

Russell Doolittle (rdoolittle  (at) ucsd.edu) and Dafei Feng, of the Section of Molecular Biology of the Division of Biological Sciences of the University of California at San Diego, released ALIGN in 1990. A version for Macintoshes was coded by Peter Markeiwicz. ALIGN implements the "progressive alignment" strategy described in their paper: Feng, D.-F. and R. F. Doolittle. 1987. Progressive sequence aligment as a prerequisite to correct phylogenetic trees. Journal of Molecular Evolution 25: 351-360. This is also the basis for the Clustal family of programs as well as the (formerly distributed) Pileup program in the GCG package. The ALIGN program can align as well as print out a tree (which does not have branch lengths). It uses Doolittle's own formats, and so three other programs are included with ALIGN to convert formats. The programs are distributed by ftp from the EBI ftp software server at ftp.ebi.ac.uk in directory pub/software/mac as file align.hqx. A set of C source programs presumably equivalent to these is also made available by Milton Saier at UCSD on a web page at http://www-biology.ucsd.edu/~msaier/transport/software.html.

Roland Fleißner of the Institut für Bioinformatik, University of Duesseldorf, Germany (fleissner  (at) cs.uni-duesseldorf.de), Dirk Metzler of the Institut für Informatik, University of Frankfurt, Germany (metzler (at) informatik.uni-frankfurt.de) and Arndt von Haeseler of the Center for Integrative Bioinformatics Vienna (arndt.von.haeseler (at) univie.ac.at) have written ALIFRITZ version 1.0. It simultaneously infers phylogenies and alignments using a model of insertions, deletions, and substitutions, using a Markov chain Monte Carlo method to sample from alignments within given phylogenies. It is described in the paper: Fleissner, R., D. Metzler, and A. von Haeseler. 2005. Simultaneous statistical multiple alignment and phylogeny reconstruction. Systematic Biology 54: 548-561. ALIFRITZ is available as C source code and as a Linux executable from its web page at http://www.cibiv.at/software/alifritz/

   Ben Redelings, currently of the National Evolutionary Synthesis Center (benjamin.redelings (at) nescent.org) and Marc Suchard of the Department of Biomathematics of the University of California, Los Angeles (msuchard (at) ucla.edu) have produced BAli-Phy (Bayesian ALIgnments and PHYlogenies), version 2.1.0, a program for joint Bayesian estimation of alignment and phylogeny. Instead of inferring trees based on a single fixed alignment, BAli-Phy considers near-optimal alignments when estimating the phylogeny. BAli-Phy can also make use of information in shared insertions or deletions to infer the phylogeny. It uses a Markov chain Monte Carlo (MCMC) sampling to draw from the posterior distribution of alignments and trees. It can provide maximum posterior probability estimates the tree and the alignment and indicate the extent of support for groups and alignment positions. It can analyze either DNA or protein sequences, allowing for rate variation among sites and allowing a variety of substitution models. It is described in the papers:

• Redelings B. D, and M. A. Suchard 2005. Joint Bayesian estimation of alignment and phylogeny, Systematic Biology 54(3): 401-418.
• Suchard, M. A. and B. D. Redelings. 2006. BAli-Phy: simultaneous Bayesian inference of alignment and phylogeny. Bioinformatics 22: 2047-2048.

Kazutaka Katoh, Hiroyuki Toh, K. Kuma, T. Miyata, and K. Misawa of the Division of Bioinformatics of the University of Kyushu, Japan (katoh (at) bioreg.kyushu-u.ac.jp.) have written MAFFT (Multiple sequence Alignment by Fast Fourier Transform), version 6.821, a fast multiple sequence alignment program using Fast Fourier Transforms and progressive alignment. MAFFT has several methods for fast progressive alignment of very large numbers of sequences, allowing for large gaps, though tending to be limited to cases in which the blocks of aligned sites stay in the same order. It can build and output a tree as one option. It is described in the paper:

• Katoh, K. and H. Toh. 2007. PartTree: an algorithm to build an approximate tree from a large number of unaligned sequences. Bioinformatics 23: 372-374.
• Katoh, K., K. Kuma, H. Toh and T. Miyata, 2005. MAFFT version 5: improvement in accuracy of multiple sequence alignment. Nucleic Acids Research 33: 511-518.
• Katoh, K., K. Misawa, K. Kuma and T. Miyata. 2002. MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform.Nucleic Acids Research 30: 3059-3066

Robert C. Edgar and Kimmen Sjolander (bob (at) drive5.com) (Sjolander is of the Department of Bioengineering of the University of California, Berkeley) have produced LOBSTER, a package carrying out Simultaneous alignment and tree construction using hidden markov models (SATCHMO), which aligns protein sequences while constructing Hidden markov Models of the alignments. It creates a hidden markov model of each protein structure, aligning sequences to a profile and constructing a tree by clustering the most similar sequences. The HMM profile constructed shows different numbers of positions as alignable as one moves through the tree, so an interactive tree viewer and sequence viewer is included to view the result. It is described, and related methods described, in the papers:

• Edgar, R. C. and K. Sjolander. 2003. SATCHMO: Sequence alignment and tree construction using hidden Markov models, Bioinformatics 19(11): 1404-1411.
• Edgar, R. C. and K. Sjolander. 2004. COACH: profile-profile alignment of protein families using hidden Markov models, Bioinformatics 20(8):1309-1318

Robert Edgar of Mill Valley, California (muscle (at) drive5.com) has written MUSCLE (Multiple Sequence Comparison by Log-Expectation), version 3.8.31, a program for creating multiple alignments of amino acid or nucleotide sequences. MUSCLE counts k-tuples shared among pairs of sequences and makes a preliminary phylogenetic tree for the sequences from this. It then makes a preliminary multiple-sequence alignment, and iteratively reconsiders the tree and the alignment. The result is many times faster than ClustalW and more accurate as well. The trees produced by the first or second tree-building procedures can be written out as well. It is described in the papers:

• Edgar, R. C. 2004. MUSCLE: multiple sequence alignment with high accuracy and high throughput, Nucleic Acids Research 32(5): 1792-1797.
• Edgar, R. C. 2004. MUSCLE: a multiple sequence alignment method with reduced time and space complexity. BMC Bioinformatics 5 113.

Manolo Gouy of the Laboratoire de Biometrie et Biologie Evolutive of the Centre National de la Recherche Scientifique, France (manolo.gouy (at) univ-lyon1.fr) has released SeaView version 4.3.3, a multiplatform graphical user interface for sequence alignment and phylogenetic tree building. SeaView allows multiple sequence alignment with the MUSCLE and ClustalW programs, and can also drive many other external multiple alignment algorithms. It also drives GBlocks to help select blocks of evolutionarily conserved sequence sites. Tree building can be done using parsimony, distance, or maximum likelihood (using PHYML) approaches. SeaView also allows network access to sequence databases, and display, printing, and copy-to-clipboard of rooted or unrooted, binary or multifurcating phylogenetic trees. Given this availability of many different methods for phylogenetic analyses, SeaView will be especially useful for teaching and for occasional users of such software. It is described in the paper: Gouy M., S. Guindon, and O. Gascuel. 2010. SeaView version 4: a multiplatform graphical user interface for sequence alignment and phylogenetic tree building. Molecular Biology and Evolution 27 (2): 221-224. It is available as C++ source code, Windows executables, Linux executables and Mac OS X universal executables, and SeaView is also available as Linux packages for Debian, Fedora, and Gentoo Linux. It can be downloaded from its web site at http://pbil.univ-lyon1.fr/software/seaview.html

Pietro Liò, of the Computer Laboratory at the University of Cambridge (Pietro.Lio  (at) cl.cam.ac.uk), has written PASSML and PASSML_TM, which use likelihood methods with Hidden Markov models to infer phylogeny and also secondary structure from protein data. PASSML is for general proteins and PASSML_TM is for membrane proteins. The methods used are described in the papers: Goldman, N., J. L. Thorne, and D. T. Jones. 1998. Assessing the impact of secondary structure and solvent accessibility on protein evolution. Genetics 149: 445-458, PASSML is described in the paper: Liò, P., N. Goldman, J. L. Thorne and D. T. Jones. 1998. PASSML: combining evolutionary inference and protein secondary structure prediction. Bioinformatics 14: 726-733, and PASSML_TM is described in the paper: Liò, P. and N. Goldman. 1999 Using protein structural information in evolutionary inference: transmembrane proteins. Molecular Biology and Evolution 16: 1696-1710. The programs are available as ANSI C source code. The source code is available via its web page at http://www.ebi.ac.uk/goldman/hmm/passml.html.

Rod Page (r.page  (at) bio.gla.ac.uk), of the Division of Environmental and Evolutionary Biology of the University of Glasgow has written COMPONENT version 2.0, a program for Windows systems for comparing cladograms for use in phylogeny and biogeography studies. It has many tree comparison and consensus methods, and far more features for biogeographic studies (such as comparing species and area cladograms) than any other package. It also can generate random trees. It runs under Windows 3.0 or higher. There is a review of the program in: Slowinksi, J. 1993. Review of Component, Version 2.0, by Roderick D. M. Page. Cladistics 9: 351-353. COMPONENT is available free from its web site at http://taxonomy.zoology.gla.ac.uk/rod/cpw.html. Source code in Pascal and documentation (as PDFs) are also available there. A very early development Macintosh version ("COMPONENT Lite") is available from the COMPONENT Lite web site at http://taxonomy.zoology.gla.ac.uk/rod/cplite/guide.html.

  Rod Page(r.page  (at) bio.gla.ac.uk), of the Division of Environmental and Evolutionary Biology of the University of Glasgow and Michael Charleston (mcharles  (at) it.usyd.edu.au) of the Biological Informatics and Technology Centre of the School of Information Technologies of the University of Sydney, Sydney, Australia have written TREEMAP, version 3, a free program for comparing host and parasite phylogenies. It allows you to interactively compare host and parasite trees, construct reconstructions of the history of the association, and perform some simple randomisation tests of hypotheses of cospeciation. It also can use Charleston's "Jungles" method to fit parasite trees to host trees by parsimony. That method is described in his paper: Charleston, M. A. 1998 Jungles: A new solution to the host/parasite phylogeny reconciliation problem. Mathematical Biosciences 149: 191-223. For a description of the method used by TreeMap, see Page, R.D.M. 1994. Parallel phylogenies: Reconstructing the history of host-parasite assemblages. Cladistics 10: 155-173. It can also estimate the number of randomized parasite trees that map as well to the host tree as does the original parasite tree. The program is available as a Java executable, which can be downloaded from its web site at http://www.it.usyd.edu.au/~mcharles/software/treemap/treemap3.html. A beta release executable for Mac OS of version 2.0, called version 2.0β, is available at the Treemap 2.0β web site at http://www.it.usyd.edu.au/~mcharles/software/treemap/treemap.html. An earlier version, 1.0, is available as an executable for Mac OS or as an executable for Windows PCs. They can be downloaded from its WWW site: http://taxonomy.zoology.gla.ac.uk/rod/treemap.html.

Fredrik Ronquist (Fredrik.Ronquist  (at) nrm.se) of the Naturhistoriska riksmuseet, Stockholm, Sweden has released DIVA version 1.2, a program for DIspersal Vicariance Analysis. It is for analyses in historical biogeography, where one is reconstructing the distribution history of a group of organisms from the distribution areas of extant species and their phylogeny. It is a parsimony-style analysis based on optimization of the numbers of dispersal and extinction events, where one assumes that speciations divide species ranges allopatrically. It does not make any assumption about the hierarchical nature of vicariance events. It was formerly available as either a Windows executable or a Mac OS executable from its web page at http://www.ebc.uu.se/systzoo/research/diva/diva.html. Currently there is some download, not well described, including perhaps source code, available from the Sourceforge site at http://diva.sourceforge.net/.

Yu Yan, of the College of Life Sciences of Sichuan University, Chengdu, China (yuyan (at) mnh.scu.edu.cn) and A. J. Harris of the Department of Botany, Oklahoma State University, Stillwater, Oklahoma, USA have produced S-DIVA (Statistical Dispersal-Vicariance Analysis), version 1.9β and 1.5c, a tool for inferring biogeographic histories. It uses statistical dispersal-vicariance analysis to check the ancestral reconstructions and evaluate the alternative ancestral areas at each node in the tree. S-DIVA provides a graphical user interface and can export high resolution graphical results for further analysis. It expands on the methods provided by DIVA by using a Bayesian approach to uncertainty in the phylogeny. It is described in a paper: Yu, Y., A. J. Harris, and X. J. He. 2010. S-DIVA (Statistical Dispersal-Vicariance Analysis): a tool for inferring biogeographic histories. Molecular Phylogenetics and Evolution 56: 848-850. It is available as a Windows executable. Microsoft .NET 2 Framework should be installed on the system to enable S-DIVA to be run. S-DIVA can be downloaded from its web site at http://mnh.scu.edu.cn/s-diva/

Fredrik Ronquist (Fredrik.Ronquist  (at) nrm.se) of the Naturhistoriska riksmuseet, Stockholm, Sweden has written TreeFitter version 1.0. It fits parasite trees to a host tree, and can also use them to infer the best host tree. The program, which has many options, uses an event-based parsimony method, which penalizes events using penalties chosen to reflect their improbability. The NEXUS file format is used for the tree files. It is available from its web site at http://www.ebc.uu.se/systzoo/research/treefitter/treefitter.html as either a Windows executable or a Mac OS executable. An on-line manual is available at the web site.

Steffen Junick, Daniel Merkle, and Martin Middendorf, of the research group on Parallel Computing and Complex Systems of the Faculty of Mathematics and Computer Science at the the Universität Leipzig, Germany (Merkle is currently in the Department of Mathematics and Computer Science at the University of Southern Denmark) (daniel (at) imada.sdu.dk) have written Tarzan (it is called this because pairs of trees that are cophylogenies have been called "Jungles"), Tarzan is in version 0.9. It is a program for the reconstruction of cophylogenies (host/parasite trees or fits of trees to biogeographic vicariance patterns). Tarzan uses an event-based method to find cost minimal or reconstructions or reconstructions that have a minimal (or maximal) number of certain evolutionary events. Five different types of evolutionary events are considered: cospeciation, duplication, sorting, switching, and extinction. For host-parasite systems cospeciation events refer to simultaneous host and parasite speciation, duplication events are independent parasite speciations, sorting events correspond to lineage sorting, and switches correspond to host shifts. It is described in the paper: Merkle, D. and M. Middendorf. 2005. Reconstruction of the cophylogenetic history of related phylogenetic trees with divergence timing information Theory in Biosciences 123(4): 277-299. Tarzan is available as Java code. It can be downloaded from its web site at http://pacosy.informatik.uni-leipzig.de/pv/Software/Tarzan/PV-Tarzan.engl.html

Pierre Legendre of the Département de Sciences Biologiques of the Université de Montréal, Montréal, Quebec (Pierre.Legendre (at) umontreal.ca) has written ParaFit, a program that tests host-parasite evolution. It tests the hypothesis of coevolution between a clade of hosts and a clade of parasites. The null hypothesis of the global test is that the evolution of the two groups, as revealed by the two phylogenetic trees and the set of host-parasite association links, has been independent. The method requires some estimates of the phylogenetic trees or phylogenetic distances, and also a description of the host-parasite associations (H-P links) observed in nature. Two types of test are produced by the program: a global test of coevolution and a test on each H-P link. It is described in the paper: Legendre, P., Y. Desdevises and E. Bazin. 2002. A statistical test for host-parasite coevolution. Systematic Biology 51(2): 217-234. It is available as FORTRAN source code, Windows executables, Powermac Mac OS X executables, and Mac OS 9 executables. It can be downloaded from its web site at http://www.bio.umontreal.ca/casgrain/en/labo/parafit.html

Alexandros Stamatakis, A. Auch, J. Meier-Kolthoff, and M. Göker , of the Laboratory for Computational Biology and Bioinformatics (LCBB) of the École Polytechnique Fédérale de Lausanne, Switzerland and of the Center for Bioinformatics (ZBIT) of the University of Tübingen, Germany and the Lehrstuhl für Spezielle Botanik und Mykologie of the Botanisches Institut, Universität Tübingen (Stamatakis is currently at Lehrstuhl XII - Machine Learning and Data Mining in Bioinformatics at the Technische Universität München, Germany) (Alexandros.Stamatakis (at) h-its,org) have written AxParafit (AleXandros's version of Parafit), a parallel version of the program ParaFit for fitting host and parasite trees. AxParafit and AxPcoords are highly optimized versions of Pierre Legendre's ParaFit and DistPCoA programs for statistical analysis of host-parasite coevolution. AxParafit has also been parallelized with MPI (Message Passing Interface) for compute clusters. The AxParafit site also includes a parallel version of the program AxPcoords which is used with AxParafit. They are described in the paper: Stamatakis, A., A. Auch, J. Meier-Kolthoff, and M. Göker. 2007. AxPcoords and Parallel AxParafit: Statistical co-phylogenetic analyses on thousands of taxa. BMC Bioinformatics 8: 405. They are available as C source code, Windows executables, Linux executables and Mac OS X universal executables. They can be downloaded from its web site at http://icwww.epfl.ch/~stamatak/AxParafit.html

Daniel Merkle, Martin Middendorf, and Nicolas Wieseke of the Department of Computer Science of the University of Leipzig, Germany (middendorf (at) informatik.uni-leipzig.de) has released CoRe-PA version 1.0, tool for reconstructing the coevolutionary history of host parasite systems. CoRe-PA is a tool for reconstructing the coevolutionary history of host parasite systems. As Tarzan it uses an event-based method to find cost minimal reconstructions. These events are cospeciation, sorting, duplication and (host)switching. With CoRe-PA you can design host parasite scenarios with a graphical editor, generate random coevolutionary scenarios using the beta-split model with beta 0, -1 or -1.5, generate random coevolutionary scenarios by simulating coevolution, generate random coevolutionary scenarios which retain the characterof given host parasite systems, handle non-binary host and parasite phylogenies, choose between different ways of handling host switches, use divergence timing information, compute the best reconstructions for a given set of costs, compute the best cost vector for a given host parasite system (where the cost vector fits best to the reconstructed event frequencies), do randomization tests for given host parasite systems to analyze the evidence for coevolution, and export host parasite scenarios and their reconstructions to SVG graphics files. It is described in the paper: Merkle, D., M. Middendorf, and N. Wieseke. 2010. A parameter-adaptive dynamic programming approach for inferring cophylogenies. BMC Bioinformatics 11 (Suppl 1): S60. It is available as Java executables, Windows executables, Linux executables and Mac OS X universal executables. It can be downloaded from its web site at http://pacosy.informatik.uni-leipzig.de/58-1-Downloads.html

Ran Libeskind-Hadas of the Computer Science of Harvey Mudd College in Claremont, California (hadas (at) cs.hmc.edu) has released Jane version 3, a cophylogeny reconstruction package. The input to Jane is a file containing a host tree, a parasite tree, and a mapping of the tips of the parasite tree to tips of the host tree. The user may specify the costs of each of five types of events: cospeciations, duplications, host switches, losses, and failure to diverge. Jane then endeavors to find least cost mappings of the parasite tree onto the host tree subject to the given tip mapping. Jane also has a features to perform randomization tests. It is described in the paper: Conow, C., D. Fielder, Y. Ovadia and R. Libeskind-Hadas. 2010. Jane: A new tool for the cophylogeny reconstruction problem. Algorithms for Molecular Biology 5: 16. It is available as Java executables. It can be downloaded from its web site at http://www.cs.hmc.edu/~hadas/jane/

  Athanasia C. Tzika, Raphaël Helaers, and Michel Milinkovitch of the Laboratory of Artificial and Natural Evolution (LANE) of the Department of Zoology and Animal Biology at the University of Geneva, Switzerland, and Yves Van de Peer, of the Department of Plant Systems Biology of the University of Gent, Belgium (info (at) mantisdb.org) or (Michel.Milinkovitch (at) unige.ch) have produced MANTiS version 1.1, a program using molecular databases to reconstruct gene duplications and losses . MANTiS builds a relational database integrating, in a phylogenetic framework, all Ensembl genes, corresponding PANTHER molecular functions and biological processes, as well as GNF, e-genetics, and HMDEG expression data. It makes use of the Ensembl ortholog/paralog prediction pipeline to reconstruct gene duplication events, and implements a dynamical programming approach for the mapping of gene gains, duplications, and losses on the phylogenetic tree.

It allows the user to identify gains and losses on specific branches of the tree, see the genome content of ancestral species, statistically over- or under-represented molecular functions, biological processes and anatomical systems (expression data), and reconstruct tissue specificity of gained, duplicated, and lost genes. It is described in the paper: Tzika, A. C., R. Helaers, Y. Van de Peer and M. C. Milinkovitch. 2008. MANTiS: a phylogenetic framework for multi-species genome comparisons. Bioinformatics 24(2): 151-157. It is available as Java executables with a Windows executable installer, a Linux executable installer, and a Mac OS X universal executable installer. It can be downloaded from its web site at http://www.mantisdb.org

   Jonathan Bollback

• Nielsen, R. 2002. Mapping mutations on phylogenies. Systematic Biology 51: 729-739.
• Huelsenbeck, J. P., R. Nielsen, and J. P. Bollback. 2003. Stochastic mapping of morphological characters. Systematic Biology 52: 131-158.
• Bollback, J. P. 2006. SIMMAP: Stochastic character mapping of discrete traits on phylogenies. BMC Bioinformatics 7:88.

Liran Carmel, Yuri I. Wolf, Igor B. Rogozin, and Eugene V. Koonin of the National Center for Biotechnology Information, National Library of Medicine of the National Institutes of Health, Bethesda, Maryland (Carmel is now at the the Department of Computer Science at Hebrew University, Jerusalem, Israel with email address  liran.carmel (at) carmellab.com) released EREM (Evolutionary Reconstruction by Expectation-Maximization), a program for parameter estimation and ancestral reconstruction for evolution of binary characters. EREM assumes a probabilistic model for evolution of binary characters on a given bifurcating tree. EREM estimates rates of change between states 0 and 1 of the model, and reconstructs ancestral states (presence and absence in internal nodes) and the location of events (gains and loss along branches). It can also be used to simulate data on a tree. It is available as C++ source code and Windows executables. It can be downloaded from its web site at http://carmelab.huji.ac.il/software/EREM/erem.html

Antonio Marco and Ignacio Marín of the Departamento de Genética of the Universitat de València and of the Instituto de Biomedicina de València, of the Consejo Superior de Investigaciones Científicas, València, Spain (marcasan (at) uv.es) have written Tree Tracker, a Perl script to detect overrepresented clusters in a tree. It takes a user-supplied tree and a list of genes. The program uses a permutation analysis of ranked clusters to test whether groups within the tree are overrepresented for having one state of genes that have two possible states. It is described in the paper: Marco, A. and I. Marín. 2007. A general strategy to determine the congruence between a hierarchical and a non-hierarchical classification. BMC Bioinformatics 8: 442. It is available as a Perl script. It can be downloaded from its web site at http://www.uv.es/~genomica/treetracker/

Jianzhi George Zhang of the Department of Ecology and Evolutionary Biology of the University of Michigan, Ann Arbor, Michigan (jianzhi (at) umich.edu) produced Ancestor, a program for inferring the ancestral protein sequence of a set of species from their protein sequences. The tree of the sequences is inferred by the minimum evolution distance matrix method of Rzhetsky and Nei. I can estimate the ancestral sequences at all nodes of the tree. The methods are described in a paper: Zhang, J., and M. Nei. 1997. Accuracies of ancestral amino acid sequences inferred by the parsimony, likelihood, and distance methods. Journal of Molecular Evolution 44: S139-S146. The program is distributed as a DOS executable with C source code. It will run in a Windows Command Prompt window. It is available from Masatoshi Nei's lab software site software site at https://homes.bio.psu.edu/people/faculty/nei/software.htm

Jianzhi George Zhang of the Department of Ecology and Evolutionary Biology of the University of Michigan, Ann Arbor, Michigan (jianzhi (at) umich.edu) has produced ANC-GENE, a program to infer ancestral protein and DNA sequences from DNA sequences of a coding gene when the phylogeny of the species is known. It first infers the amino acids by a distance-based Bayesian method, and then infers the underlying nucleotide sequences by fixing the inferred amino acids. It estimates branch lengths on the phylogeny by a distance method before inferring the ancestral sequences. It uses one of two possible models of amino acid changes (the Poisson-f or JTT-f models), as well as the Jukes-Cantor model of nucleotide substitution. It outputs both inferred pathways of change at each amino acid position and inferred sequences at each node of the tree. The methods are discussed in' this paper: Zhang, J., and M. Nei. 1997. Accuracies of ancestral amino acid sequences inferred by the parsimony, likelihood, and distance methods. Journal of Molecular Evolution 44 (Suppl 1): S139-S146. ANC-GENE is available as a DOS executable and C souce code. These can be executed in Windows in a Command Prompt windows. It can be downloaded from the Nei laboratory software web site at https://homes.bio.psu.edu/people/faculty/nei/software.htm

Xun Gu, of the Department of Genetics, Development and Cell Biology and the Center for Bioinformatics and Biological Statistics at Iowa State University, Ames, Iowa (xgu  (at) iastate.edu) has release Mgenome version 1.0. It finds trees for multiple genome rearrangement by signed reversals. For a collection of genomes represented by signed permutations of genes, it finds a tree that connects all given genomes by reversal paths such that the number of all signed reversals is as small as possible. The methods seem to be described in a paper: Wu, S., and X. Gu. 2003. Algorithms for multiple genome rearrangement by signed reversals. Pacfic Symposium on Biocomputing 8: 363-74, although the paper does not refer to the program. The paper is available as a PDF at the Gu lab web site. The program is available as a Windows executable at the Gu lab software web site at http://xungulab.com/software.html.

Mathieu Blanchette, of the School of Computer Science, McGill University, Montréal, Québec (blanchem  (at) mcb.mcgill.edu) has written BPAnalysis, a program that infers phylogenies from a set of gene orders by minimizing the number of breakpoints required in genome rearrangement (this is not the same as minimizing the number of rearrangement events). It is a C++ program which is also distributed in source code and in an executable for DOS and Windows. The method employed is described in the paper: Sankoff, D. and M. Blanchette. 1998. Multiple genome rearrangement and breakpoint phylogeny. Journal of Computational Biology 5: 555-570. It is available from Blanchette's software page at http://www.mcb.mcgill.ca/~blanchem/software.html

   Benjamin Vernot, Aiton Goldman and Dannie Durand of the Departments of Biological Sciences and Computer Science of the Carnegie Mellon University, Pittsburgh, Pennsylvania (notung (at) cs.cmu.edu) have released Notung version 2.6, a unified framework for incorporating gene duplication/loss parsimony in phylogenetic inference. Given a gene and species tree as input, Notung can: (1) Reconcile the trees, (2) Estimate upper and lower bounds on duplication times in terms of speciation events, (3) Root an unrooted tree by minimizing gene duplications and losses, and (4) Rearrange regions of a gene tree with weak support in the sequence data to obtain alternate hypotheses. Notung's graphical user interface supports exploratory data analysis of very large trees and rapid review of many alternate hypotheses. Notung also provides a command-line interface for automated analysis of many trees in high-throughput genomic studies. Notung can read and save trees in Newick, NHX, or Notung file format. Images can be outputted in PNG format for use in publications. Notung is freely available in a Java executable which can run on Mac OS X, Windows and Linux systems. The distribution includes: Notung java executable, a manual in PDF format with worked examples, sample trees, sample scripts for automated analysis. Java 1.4 or higher is required. It is described in the paper: Durand, D., B. V. Halldorsson, and B. Vernot. 2005. A hybrid micro-macroevolutionary approach to gene tree reconstruction. Journal of Computational Biology 13(2): 320-335. It can be downloaded from its web site at http://www.cs.cmu.edu/~durand/Notung/

Olivier Elemento, then of the IMGT, the International imMunoGeneTics database and the LIRMM (Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier) of the Université de Montpellier II, Montpellier, France (He is now at the Institute for Computational Biomedicine at Weill Cornell Medical College in New York City and his email address is ole2001 (at) med.cornell.edu) has written DTscore (Duplication, Tandem - score), a distance-based tandem duplication tree reconstruction program. It takes as input a distance matrix between copies in a family of tandem repeats. The rows and columns need to be ordered in the same way as the copies are in the locus. DTscore can be applied to relatively large datasets (more than a hundred copies). It is described in the paper: Elemento O. and O. Gascuel. 2002. A fast and accurate distance algorithm to reconstruct tandem duplication trees. Bioinformatics 18: S92-S99. It is available as C source code, Windows executables and Linux executables. It can be downloaded from its web page at http://www.lirmm.fr/%7Eelemento/DTscore/  and also at its web site at ATGC at http://www.atgc-montpellier.fr/dtscore/binaries.php

Michael Sanderson of the Department of Ecology and Evolutionary Biology of the University of Arizona, Tucson, Arizona (sanderm (at) email.arizona.edu) has written gtp (Gene Tree Parsimony), version 0.15, a program to reconcile gene trees with species trees using a gene tree parsimony criterion. The program reads a NEXUS-format file containing the species tree and a series of gene trees, which have at their tips the names of the species. The gene trees are reconciled with the species trees using a gene duplication count. The gene trees can either be considered to be rooted as given, or optionally they can be considered to be unrooted, in which case the count of duplications is made by considering the minimum over all possible rootings of each gene tree. The methods are described in the paper: Zmasek, C. M. and S. R. Eddy. 2001. A simple algorithm to infer gene duplication and speciation events on a gene tree. Bioinformatics 17: 821-828. It is available as C source code. It can be downloaded from its web site at http://loco.biosci.arizona.edu/gtp/gtp.html

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