Approximate Maximum Parsimony and Ancestral Maximum Likelihood

We explore the maximum parsimony (MP) and ancestral maximum likelihood (AML) criteria in phylogenetic tree reconstruction. Both problems are NP-hard, so we seek approximate solutions. We formulate the two problems as Steiner tree problems under appropriate distances. The gist of our approach is the succinct characterization of Steiner trees for a small number of leaves for the two distances. This enables the use of known Steiner tree approximation algorithms. The approach leads to a 16/9 approximation ratio for AML and asymptotically to a 1.55 approximation ratio for MP.     

Shrinkage Effect in Ancestral Maximum Likelihood

Ancestral maximum likelihood (AML) is a method that simultaneously reconstructs a phylogenetic tree and ancestral sequences from extant data (sequences at the leaves). The tree and ancestral sequences maximize the probability of observing the given data under a Markov model of sequence evolution, in which branch lengths are also optimized but constrained to take the same value on any edge across all sequence sites. AML differs from the more usual form of maximum likelihood (ML) in phylogenetics because ML averages over all possible ancestral sequences. ML has long been know to be statistically consistent - that is, it converges on the correct tree with probability approaching 1 as the sequence length grows. However, the statistical consistency of AML has not been formally determined, despite informal remarks in a literature that dates back 20 years. In this short note we prove a general result that implies that AML is statistically inconsistent. In particular we show that AML can 'shrink' short edges in a tree, resulting in a tree that has no internal resolution as the sequence length grows. Our results apply to any number of taxa.     

Molecular phylogeny of oribatid mites (Oribatida, Acari): evidence for multiple radiations of parthenogenetic lineages

Nucleotide sequences of the D3 expansion segment and its flanking regions of the 28S rDNA gene were used to evaluate phylogenetic relationships among representative sexual and asexual oribatid mites (Oribatida, Acariformes). The aim of this study was to investigate the hypothesis that oribatid mites consist of species-rich clusters of asexual species that may have radiated while being parthenogenetic. Furthermore, the systematic position of the astigmate mites (Astigmata, Acariformes) which have been hypothesised to represent a paedomorphic lineage within the oribatid mites, is investigated. This is the first phylogenetic tree for oribatid mites s.l. (incl. Astigmata) based on nucleotide sequences. Intraspecific genetic variation in the D3 region was very low, confirming the hypothesis that this region is a good species marker. Results from neighbour joining (NJ) and maximum parsimony (MP) algorithms indicate that several species-rich parthenogenetic groups like Camisiidae, Nanhermanniidae and Malaconothridae are monophyletic, consistent with the hypothesis that some oribatid mite groups diversified despite being parthenogenetic. The MP and maximum likelihood (ML) method indicated that the D3 region is a good tool for elucidating the relationship of oribatid mite species on a small scale(genera, families) but is not reliable for large-scale taxonomy, because branches from the NJ algorithm collapsed in the MP and ML tree. In all trees calculated by different algorithms the Astigmata clustered within the oribatid mites, as proposed earlier.     

Evolutionary Triplet Models of Structured RNA

The reconstruction and synthesis of ancestral RNAs is a feasible goal for paleogenetics. This will require new bioinformatics methods, including a robust statistical framework for reconstructing histories of substitutions, indels and structural changes. We describe a “transducer composition” algorithm for extending pairwise probabilistic models of RNA structural evolution to models of multiple sequences related by a phylogenetic tree. This algorithm draws on formal models of computational linguistics as well as the 1985 protosequence algorithm of David Sankoff. The output of the composition algorithm is a multiple-sequence stochastic context-free grammar. We describe dynamic programming algorithms, which are robust to null cycles and empty bifurcations, for parsing this grammar. Example applications include structural alignment of non-coding RNAs, propagation of structural information from an experimentally-characterized sequence to its homologs, and inference of the ancestral structure of a set of diverged RNAs. We implemented the above algorithms for a simple model of pairwise RNA structural evolution; in particular, the algorithms for maximum likelihood (ML) alignment of three known RNA structures and a known phylogeny and inference of the common ancestral structure. We compared this ML algorithm to a variety of related, but simpler, techniques, including ML alignment algorithms for simpler models that omitted various aspects of the full model and also a posterior-decoding alignment algorithm for one of the simpler models. In our tests, incorporation of basepair structure was the most important factor for accurate alignment inference; appropriate use of posterior-decoding was next; and fine details of the model were least important. Posterior-decoding heuristics can be substantially faster than exact phylogenetic inference, so this motivates the use of sum-over-pairs heuristics where possible (and approximate sum-over-pairs). For more exact probabilistic inference, we discuss the use of transducer composition for ML (or MCMC) inference on phylogenies, including possible ways to make the core operations tractable.     

Phylogenetic relationships between the six superoxide dismutase proteins (FeSOD) of Trichomonas vaginalis and FeSOD6 genetic diversity

The parasitic protozoan Trichomonas vaginalis is known to contain several types of Fe-containing superoxide dismutase proteins (FeSOD). Using three different methods of phylogenetic analysis, maximum parsimony (MP), neighbor joining (NJ), and maximum likelihood (ML) methods, we examined the phylogenetic relationships among the six FeSOD (FeSOD1-FeSOD6) based on their amino acid sequences. All the analyses consistently suggested that the six proteins formed a monophyletic group implying that they probably be originated from an ancestral protein form through repeated duplication events. Although MP tree was totally unresolved, the NJ and ML trees revealed that FeSOD6 placed the most basal position and thus emerged earlier than the other five gene types during the evolution of T. vaginalis. Phylogenetic relationships among the five remaining proteins were (FeSOD2, FeSOD3), (FeSOD4, (FeSOD1, FeSOD5)) although weakly supported in terms of bootstrapping values. In addition to this, we newly designed two PCR primer specifically amplifying full-length FeSOD6 gene and examined its genetic diversity among 12 T. vaginalis isolates from five countries and three continents. They had the same nucleotide sequences except those of three Korean isolates which showed one to three different nucleotides.     

Phylogeny of the basal angiosperm genus Pseuduvaria (Annonaceae) inferred from five chloroplast DNA regions, with interpretation of morphological character evolution

Phylogenetic relationships within the magnoliid basal angiosperm genus Pseuduvaria (Annonaceae) are investigated using chloroplast DNA sequences from five regions: psbA-trnH spacer, trnL-F, matK, rbcL, and atpB-rbcL spacer. Over 4000 nucleotides from 51 species (of the total 53) were sequenced. The five cpDNA datasets were analyzed separately and in combination using maximum parsimony (MP), maximum likelihood (ML), and Bayesian methods. The phylogenetic trees constructed using all three phylogenetic methods, based on the combined data, strongly support the monophyly of Pseuduvaria following the inclusion of Craibella phuyensis. The trees generated using MP were less well resolved, but relationships are similar to those obtained using the other methods. ML and Bayesian analyses recovered trees with short branch lengths, showing five main clades. This study highlights the evolutionary changes in seven selected morphological characters (floral sex, stamen and carpel numbers, inner petal color, presence of inner petal glands, flowering peduncle length, and monocarp size). Although floral unisexuality is ancestral within the genus, several evolutionary lineages reveal reversal to bisexuality. Other phylogenetic transitions include the evolution of sapromyophily, and fruit-bat frugivory and seed dispersal, thus allowing a wide range of adaptations for species survival.     

Robustness of ancestral state estimates: evolution of life history strategy in ichneumonoid parasitoids

We test hypotheses for the evolution of a life history trait among a group of parasitoid wasps (Hymenoptera: Ichneumonoidea), namely, the transition among koinobiont parasitoids (parasitoids whose hosts continue development after oviposition) between attacking exposed hosts and attacking hosts that are concealed within plant tissue. Using a range of phylogeny estimates based on 28S rDNA sequences, we use maximum parsimony (MP) and maximum likelihood (ML) methods to estimate the ancestral life history traits for the main clades in which both traits occur (using the programs MacClade and Discrete, respectively). We also assess the robustness of these estimates; for MP, we use step matrices in PAUP* to find the minimum weight necessary to reverse estimates or make them ambiguous, and for ML, we measure the differences in likelihood after fixing the ancestral nodes at the alternative states. We also measure the robustness of the MP ancestral state estimate against uncertainties in the phylogeny estimate, manipulating the most-parsimonious tree in MacClade to find the shortest suboptimal tree in which the ancestral state estimate is reversed or made ambiguous. Using these methods, we find strong evidence supporting two transitions among koinobiont Ichneumonoidea: (1) to attacking exposed hosts in a clade consisting of the Helconinae and related subfamilies, and (2) the reverse transition in a clade consisting of the Euphorinae and related subfamilies. In exploring different methods of analyzing variable-length DNA sequences, we found that direct optimization with POY gave some clearly erroneous results that had a profound effect on the overall phylogeny estimate. We also discuss relationships within the superfamily and expand the Mesostoinae to include all the gall-associated braconids that form the sister group of the Aphidiinae.     

基于孕激素受体基因的类人猿亚目的分子系统学研究

通过对类人猿亚目中部分种类的孕激素受体基因进行分析,重建类人猿亚目的 系统发育关系.扩增并测定了来源于14个属的类人猿亚目物种的孕激素受体编码区序列,并基于这一序列数据,分别采用邻接法、最大简约法和最大似然法重建了系统发育关系.除了阔鼻下目,3种方法构建的系统发生树的拓扑结构类似且各节点支持率高.重建的人猿超科和猴超科内部亲缘关系支持多数人所认可的分类系统.本研究为黑猩猩和人的姐妹群关系提供了证据,提示黑猩猩比大猩猩或其他猿猴更接近人类.阔鼻下目中蜘蛛猴科、卷尾猴科和僧面猴科三者之间的系统发育关系在本研究中未得到很好辨析.     

Efficiencies of different genes and different tree-building methods in recovering a known vertebrate phylogeny

The relative efficiencies of different protein-coding genes of the mitochondrial genome and different tree-building methods in recovering a known vertebrate phylogeny (two whale species, cow, rat, mouse, opossum, chicken, frog, and three bony fish species) was evaluated. The tree-building methods examined were the neighbor joining (NJ), minimum evolution (ME), maximum parsimony (MP), and maximum likelihood (ML), and both nucleotide sequences and deduced amino acid sequences were analyzed. Generally speaking, amino acid sequences were better than nucleotide sequences in obtaining the true tree (topology) or trees close to the true tree. However, when only first and second codon positions data were used, nucleotide sequences produced reasonably good trees. Among the 13 genes examined, Nd5 produced the true tree in all tree-building methods or algorithms for both amino acid and nucleotide sequence data. Genes Cytb and Nd4 also produced the correct tree in most tree-building algorithms when amino acid sequence data were used. By contrast, Co2, Nd1, and Nd41 showed a poor performance. In general, large genes produced better results, and when the entire set of genes was used, all tree-building methods generated the true tree. In each tree-building method, several distance measures or algorithms were used, but all these distance measures or algorithms produced essentially the same results. The ME method, in which many different topologies are examined, was no better than the NJ method, which generates a single final tree. Similarly, an ML method, in which many topologies are examined, was no better than the ML star decomposition algorithm that generates a single final tree. In ML the best substitution model chosen by using the Akaike information criterion produced no better results than simpler substitution models. These results question the utility of the currently used optimization principles in phylogenetic construction. Relatively simple methods such as the NJ and ML star decomposition algorithms seem to produce as good results as those obtained by more sophisticated methods. The efficiencies of the NJ, ME, MP, and ML methods in obtaining the correct tree were nearly the same when amino acid sequence data were used. The most important factor in constructing reliable phylogenetic trees seems to be the number of amino acids or nucleotides used.      

Rational Disagreements in Phylogenetics

This paper addresses the general problem of how to rationally choose an algorithm for phylogenetic inference. Specifically, the controversy between maximum likelihood (ML) and maximum parsimony (MP) perspectives is reframed within the philosophical issue of theory choice. A Kuhnian approach in which rationality is bounded and value-laden is offered and construed through the notion of a Style of Modeling. A Style is divided into four stages: collecting remnant models, constructing models of taxonomical identity, implementing modeling algorithms, and finally inferring and confirming evolutionary trees or cladograms. The identification and investigation of styles is useful for exploring sociological and epistemological issues such as individuating scientific communities and assessing the rationality of algorithm choice. Regarding the last point, this paper suggests that the values motivating ML and MP perspectives are justified but only contextually; these algorithms also have normative force because they can be therapeutic by allowing us to rationally choose among several competing trees, nonetheless this force is limited and cannot be used in order to decide the controversy tout court.     

Reanalysis of Murphy et al.'s data gives various mammalian phylogenies and suggests overcredibility of Bayesian trees

Murphy and colleagues reported that the mammalian phylogeny was resolved by Bayesian phylogenetics. However, the DNA sequences they used had many alignment gaps and undetermined nucleotide sites. We therefore reanalyzed their data by minimizing unshared nucleotide sites and retaining as many species as possible (13 species). In constructing phylogenetic trees, we used the Bayesian, maximum likelihood (ML), maximum parsimony (MP), and neighbor-joining (NJ) methods with different substitution models. These trees were constructed by using both protein and DNA sequences. The results showed that the posterior probabilities for Bayesian trees were generally much higher than the bootstrap values for ML, MP, and NJ trees. Two different Bayesian topologies for the same set of species were sometimes supported by high posterior probabilities, implying that two different topologies can be judged to be correct by Bayesian phylogenetics. This suggests that the posterior probability in Bayesian analysis can be excessively high as an indication of statistical confidence and therefore Murphy et al.'s tree, which largely depends on Bayesian posterior probability, may not be correct.     

Phylogenetic relationships of agaric fungi based on nuclear large subunit ribosomal DNA sequences

Phylogenetic relationships of mushrooms and their relatives within the order Agaricales were addressed by using nuclear large subunit ribosomal DNA sequences. Approximately 900 bases of the 5' end of the nucleus-encoded large subunit RNA gene were sequenced for 154 selected taxa representing most families within the Agaricales. Several phylogenetic methods were used, including weighted and equally weighted parsimony (MP), maximum likelihood (ML), and distance methods (NJ). The starting tree for branch swapping in the ML analyses was the tree with the highest ML score among previously produced MP and NJ trees. A high degree of consensus was observed between phylogenetic estimates obtained through MP and ML. NJ trees differed according to the distance model that was used; however, all NJ trees still supported most of the same terminal groupings as the MP and ML trees did. NJ trees were always significantly suboptimal when evaluated against the best MP and ML trees, by both parsimony and likelihood tests. Our analyses suggest that weighted MP and ML provide the best estimates of Agaricales phylogeny. Similar support was observed between bootstrapping and jackknifing methods for evaluation of tree robustness. Phylogenetic analyses revealed many groups of agaricoid fungi that are supported by moderate to high bootstrap or jackknife values or are consistent with morphology-based classification schemes. Analyses also support separate placement of the boletes and russules, which are basal to the main core group of gilled mushrooms (the Agaricineae of Singer). Examples of monophyletic groups include the families Amanitaceae, Coprinaceae (excluding Coprinus comatus and subfamily Panaeolideae), Agaricaceae (excluding the Cystodermateae), and Strophariaceae pro parte (Stropharia, Pholiota, and Hypholoma); the mycorrhizal species of Tricholoma (including Leucopaxillus, also mycorrhizal); Mycena and Resinomycena; Termitomyces, Podabrella, and Lyophyllum; and Pleurotus with Hohenbuehelia. Several groups revealed by these data to be nonmonophyletic include the families Tricholomataceae, Cortinariaceae, and Hygrophoraceae and the genera Clitocybe, Omphalina, and Marasmius. This study provides a framework for future systematics studies in the Agaricales and suggestions for analyzing large molecular data sets.     

New approaches to phylogenetic tree search and their application to large numbers of protein alignments

Phylogenetic tree estimation plays a critical role in a wide variety of molecular studies, including molecular systematics, phylogenetics, and comparative genomics. Finding the optimal tree relating a set of sequences using score-based (optimality criterion) methods, such as maximum likelihood and maximum parsimony, may require all possible trees to be considered, which is not feasible even for modest numbers of sequences. In practice, trees are estimated using heuristics that represent a trade-off between topological accuracy and speed. I present a series of novel algorithms suitable for score-based phylogenetic tree reconstruction that demonstrably improve the accuracy of tree estimates while maintaining high computational speeds. The heuristics function by allowing the efficient exploration of large numbers of trees through novel hill-climbing and resampling strategies. These heuristics, and other computational approximations, are implemented for maximum likelihood estimation of trees in the program Leaphy, and its performance is compared to other popular phylogenetic programs. Trees are estimated from 4059 different protein alignments using a selection of phylogenetic programs and the likelihoods of the tree estimates are compared. Trees estimated using Leaphy are found to have equal to or better likelihoods than trees estimated using other phylogenetic programs in 4004 (98.6%) families and provide a unique best tree that no other program found in 1102 (27.1%) families. The improvement is particularly marked for larger families (80 to 100 sequences), where Leaphy finds a unique best tree in 81.7% of families.     

基于线粒体Cyt b基因和CO I基因序列研究豹蛱蝶亚科(鳞翅目,蛱蝶科)10属间的系统发生关系

测定了国产豹蛱蝶亚科10属共10个代表种的Cyt 6基因和CO Ⅰ基因的部分序列.结合从GenBank中获得的3个种类CO Ⅰ基因的同源序列,以锯眼蝶亚科2个物种为外群,通过遗传分析软件对CO Ⅰ、Cyt b独立基因序列和联合基因序列以及编码的氨基酸序列进行了比较分析,同时用邻接法(NJ)、最大简约法(MP)、最大似然法(ML)和贝叶斯法(BI)重建分子系统树,分析了该亚科10个属之间的系统发生关系.结果显示:1)联合基因序列的A+T平均含量为71.90h,具A、T偏倚性,其编码的357个氨基酸中没有半胱氨酸,变异率为11.5%;2)豹蛱蝶亚族为单系群;3)青豹蛱蝶属和豹蛱蝶属间、黄襟蛱蝶属和珐蛱蝶属间具有较近的亲缘关系;4)支持将文蛱蝶属、襟蛱蝶属和珐蛱蝶属从豹蛱蝶亚科中分离出来.     

Molecular Phylogeny of the Genus Paramesotriton (Caudata: Salamandridae)

To elucidate the phylogeny of the genus Paramesotriton (Caudata: Salamandridae), we investigated three mitochondrial DNA gene fragments (1207 bp in total) of cytochrome b, ND2, and ND4 for its six recognized species. The phylogenetic relationships within Paramesotriton were reconstructed by maximum parsimony (MP) and maximum likelihood (ML) methods. Phylogenetic trees (MP and ML trees) that were constructed from the combined data set of the three gene fragments indicated that all six species of Paramesotriton formed a monophyletic group, with P. caudopunctatus as basal to the other five species. This result suggests that P. fuzhongensis is a valid species in Paramesotriton.     

Treelength optimization for phylogeny estimation

The standard approach to phylogeny estimation uses two phases, in which the first phase produces an alignment on a set of homologous sequences, and the second phase estimates a tree on the multiple sequence alignment. POY, a method which seeks a tree/alignment pair minimizing the total treelength, is the most widely used alternative to this two-phase approach. The topological accuracy of trees computed under treelength optimization is, however, controversial. In particular, one study showed that treelength optimization using simple gap penalties produced poor trees and alignments, and suggested the possibility that if POY were used with an affine gap penalty, it might be able to be competitive with the best two-phase methods. In this paper we report on a study addressing this possibility. We present a new heuristic for treelength, called BeeTLe (Better Treelength), that is guaranteed to produce trees at least as short as POY. We then use this heuristic to analyze a large number of simulated and biological datasets, and compare the resultant trees and alignments to those produced using POY and also maximum likelihood (ML) and maximum parsimony (MP) trees computed on a number of alignments. In general, we find that trees produced by BeeTLe are shorter and more topologically accurate than POY trees, but that neither POY nor BeeTLe produces trees as topologically accurate as ML trees produced on standard alignments. These findings, taken as a whole, suggest that treelength optimization is not as good an approach to phylogenetic tree estimation as maximum likelihood based upon good alignment methods.     

Efficiencies of fast algorithms of phylogenetic inference under the criteria of maximum parsimony, minimum evolution, and maximum likelihood when a large number of sequences are used

In phylogenetic inference by maximum-parsimony (MP), minimum-evolution (ME), and maximum-likelihood (ML) methods, it is customary to conduct extensive heuristic searches of MP, ME, and ML trees, examining a large number of different topologies. However, these extensive searches tend to give incorrect tree topologies. Here we show by extensive computer simulation that when the number of nucleotide sequences (m) is large and the number of nucleotides used (n) is relatively small, the simple MP or ML tree search algorithms such as the stepwise addition (SA) plus nearest neighbor interchange (NNI) search and the SA plus subtree pruning regrafting (SPR) search are as efficient as the extensive search algorithms such as the SA plus tree bisection-reconnection (TBR) search in inferring the true tree. In the case of ME methods, the simple neighbor-joining (NJ) algorithm is as efficient as or more efficient than the extensive NJ+TBR search. We show that when ME methods are used, the simple p distance generally gives better results in phylogenetic inference than more complicated distance measures such as the Hasegawa-Kishino-Yano (HKY) distance, even when nucleotide substitution follows the HKY model. When ML methods are used, the simple Jukes-Cantor (JC) model of phylogenetic inference generally shows a better performance than the HKY model even if the likelihood value for the HKY model is much higher than that for the JC model. This indicates that at least in the present case, selecting of a substitution model by using the likelihood ratio test or the AIC index is not appropriate. When n is small relative to m and the extent of sequence divergence is high, the NJ method with p distance often shows a better performance than ML methods with the JC model. However, when the level of sequence divergence is low, this is not the case.     

Efficient likelihood computations with nonreversible models of evolution

Recent advances in heuristics have made maximum likelihood phylogenetic tree estimation tractable for hundreds of sequences. Noticeably, these algorithms are currently limited to reversible models of evolution, in which Felsenstein's pulley principle applies. In this paper we show that by reorganizing the way likelihood is computed, one can efficiently compute the likelihood of a tree from any of its nodes with a nonreversible model of DNA sequence evolution, and hence benefit from cutting-edge heuristics. This computational trick can be used with reversible models of evolution without any extra cost. We then introduce nhPhyML, the adaptation of the nonhomogeneous nonstationary model of Galtier and Gouy (1998; Mol. Biol. Evol. 15:871-879) to the structure of PhyML, as well as an approximation of the model in which the set of equilibrium frequencies is limited. This new version shows good results both in terms of exploration of the space of tree topologies and ancestral G+C content estimation. We eventually apply it to rRNA sequences slowly evolving sites and conclude that the model and a wider taxonomic sampling still do not plead for a hyperthermophilic last universal common ancestor.     

Ancestral sequence reconstruction in primate mitochondrial DNA: compositional bias and effect on functional inference

Reconstruction of ancestral DNA and amino acid sequences is an important means of inferring information about past evolutionary events. Such reconstructions suggest changes in molecular function and evolutionary processes over the course of evolution and are used to infer adaptation and convergence. Maximum likelihood (ML) is generally thought to provide relatively accurate reconstructed sequences compared to parsimony, but both methods lead to the inference of multiple directional changes in nucleotide frequencies in primate mitochondrial DNA (mtDNA). To better understand this surprising result, as well as to better understand how parsimony and ML differ, we constructed a series of computationally simple "conditional pathway" methods that differed in the number of substitutions allowed per site along each branch, and we also evaluated the entire Bayesian posterior frequency distribution of reconstructed ancestral states. We analyzed primate mitochondrial cytochrome b (Cyt-b) and cytochrome oxidase subunit I (COI) genes and found that ML reconstructs ancestral frequencies that are often more different from tip sequences than are parsimony reconstructions. In contrast, frequency reconstructions based on the posterior ensemble more closely resemble extant nucleotide frequencies. Simulations indicate that these differences in ancestral sequence inference are probably due to deterministic bias caused by high uncertainty in the optimization-based ancestral reconstruction methods (parsimony, ML, Bayesian maximum a posteriori). In contrast, ancestral nucleotide frequencies based on an average of the Bayesian set of credible ancestral sequences are much less biased. The methods involving simpler conditional pathway calculations have slightly reduced likelihood values compared to full likelihood calculations, but they can provide fairly unbiased nucleotide reconstructions and may be useful in more complex phylogenetic analyses than considered here due to their speed and flexibility. To determine whether biased reconstructions using optimization methods might affect inferences of functional properties, ancestral primate mitochondrial tRNA sequences were inferred and helix-forming propensities for conserved pairs were evaluated in silico. For ambiguously reconstructed nucleotides at sites with high base composition variability, ancestral tRNA sequences from Bayesian analyses were more compatible with canonical base pairing than were those inferred by other methods. Thus, nucleotide bias in reconstructed sequences apparently can lead to serious bias and inaccuracies in functional predictions.     

MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods

Comparative analysis of molecular sequence data is essential for reconstructing the evolutionary histories of species and inferring the nature and extent of selective forces shaping the evolution of genes and species. Here, we announce the release of Molecular Evolutionary Genetics Analysis version 5 (MEGA5), which is a user-friendly software for mining online databases, building sequence alignments and phylogenetic trees, and using methods of evolutionary bioinformatics in basic biology, biomedicine, and evolution. The newest addition in MEGA5 is a collection of maximum likelihood (ML) analyses for inferring evolutionary trees, selecting best-fit substitution models (nucleotide or amino acid), inferring ancestral states and sequences (along with probabilities), and estimating evolutionary rates site-by-site. In computer simulation analyses, ML tree inference algorithms in MEGA5 compared favorably with other software packages in terms of computational efficiency and the accuracy of the estimates of phylogenetic trees, substitution parameters, and rate variation among sites. The MEGA user interface has now been enhanced to be activity driven to make it easier for the use of both beginners and experienced scientists. This version of MEGA is intended for the Windows platform, and it has been configured for effective use on Mac OS X and Linux desktops. It is available free of charge from http://www.megasoftware.net.