CiteULike: aprasad's library [491 articles]

The Chromosomal Polymorphism Linked to Variation in Social Behavior in the White-Throated Sparrow (Zonotrichia albicollis) Is a Complex Rearrangement and Suppressor of Recombination

James Thomas — 2008-07-23T18:11:09-00:00

Genetics, Vol. 179, No. 3. (1 July 2008), pp. 1455-1468.

Variation in social behavior and plumage in the white-throated sparrow (Zonotrichia albicollis) is linked to an inversion polymorphism on chromosome 2. Here we report the results of our comparative cytogenetic mapping efforts and population genetics studies focused on the genomic characterization of this balanced chromosomal polymorphism. Comparative chromosome painting and cytogenetic mapping of 15 zebra finch BAC clones to the standard (ZAL2) and alternative (ZAL2m) arrangements revealed that this chromosome is orthologous to chicken chromosome 3, and that at a minimum, ZAL2 and ZAL2m differ by a pair of included pericentric inversions that we estimate span at least 98 Mb. Population-based sequencing and genotyping of multiple loci demonstrated that ZAL2m suppresses recombination in the heterokaryotype and is evolving as a rare nonrecombining autosomal segment of the genome. In addition, we estimate that the first inversion within the ZAL2m arrangement originated 2.2 +/- 0.3 million years ago. Finally, while previously recognized as a genetic model for the evolution of social behavior, we found that the ZAL2/ZAL2m polymorphism also shares genetic and phenotypic features with the mouse t complex and we further suggest that the ZAL2/ZAL2m polymorphism is a heretofore unrecognized model for the early stages of sex chromosome evolution. 10.1534/genetics.108.088229

Comparative physical mapping: Universal overgo hybridization probe design and BAC library hybridization.

JW Thomas — 2008-07-20T20:27:59-00:00

Methods in molecular biology (Clifton, N.J.), Vol. 422 (2008), pp. 119-132.

Comparative genomics is a powerful approach for inferring the history and function of genomic sequence. The generation of bacterial artificial chromosome (BAC)-based physical maps is a proven method for the targeted comparative genomic analysis of genes or regions of interest. 'Universal' overgo hybridization probes can be used for the efficient construction of BAC-based physical maps of orthologous chromosome segments from multiple species in parallel. 'Universal' overgo hybridization probes can therefore facilitate the assembly of deep and diverse collections of experimental and computational comparative genomic resources corresponding to specific segments of the genome. The design of 'universal' overgo probes is dependent on the presence of sequences that are highly conserved within a group of species. Such conserved sequences can be readily identified using local-or whole-genome interspecies sequence alignments. Once 'universal' overgo hybridization probes are designed, simple and uniform labeling and hybridization conditions can be carried out to exploit the utility of these probes for targeted comparative physical mapping.

Coexpression of Linked Genes in Mammalian Genomes Is Generally Disadvantageous

Ben-Yang Liao — 2008-07-16T23:31:38-00:00

Mol Biol Evol, Vol. 25, No. 8. (1 August 2008), pp. 1555-1565.

Similarity in gene expression pattern between closely linked genes is known in several eukaryotes. Two models have been proposed to explain the presence of such coexpression patterns. The adaptive model assumes that coexpression is advantageous and is established by relocation of initially unlinked but coexpressed genes, whereas the neutral model asserts that coexpression is a type of leaky expression due to similar expressional environments of linked genes, but is neither advantageous nor detrimental. However, these models are incompatible with several empirical observations. Here, we propose that coexpression of linked genes is a form of transcriptional interference that is disadvantageous to the organism. We show that even distantly linked genes that are tens of megabases away exhibit significant coexpression in the human genome. However, the linkage is more likely to be broken during evolution between genes of high coexpression than those of low coexpression and the breakage of linkage reduces gene coexpression. These results support our hypothesis that coexpression of linked genes in mammalian genomes is generally disadvantageous, implying that many mammalian genes may never reach their optimal expression pattern due to the interference of their genomic environment and that such transcriptional interference may be a force promoting recurrent relocation of genes in the genome. 10.1093/molbev/msn101

Automated mapping of large-scale chromatin structure in ENCODE.

Heng Lian — 2008-07-03T21:27:08-00:00

Bioinformatics (Oxford, England) (30 June 2008)

MOTIVATION: A recently developed DNase I assay has given us our first genome-wide view of chromatin structure. In addition to cataloging DNase I hypersensitive sites, these data allows us to more completely characterize overall features of chromatin accessibility. We employed a Bayesian hierarchical change point model (CPM), a generalization of a hidden Markov Model, to characterize tiled microarray DNase I sensitivity data available from the ENCODE project. RESULTS: Our analysis shows that the accessibility of chromatin to cleavage by DNase I is well described by a four state model of local segments with each state described by a continuous mixture of Gaussian variables. The CPM produces a better fit to the observed data than the HMM. The large posterior probability for the fourstate CPM suggests that the data falls naturally into four classes of regions, which we call major and minor DNase I hypersensitive sites (DHSs), regions of intermediate sensitivity, and insensitive regions. These classes agree well with a model of chromatin in which local disruptions (DHSs) are concentrated within larger domains of intermediate sensitivity, the accessibility islands. The CPM assigns 92% of the bases within the ENCODE regions to the insensitive regions. The 5.8% of the bases that are in regions of intermediate sensitivity are clearly enriched in functional elements, including genes and activating histone modifications, while the remaining 2.2% of the bases in hypersensitive regions are very strongly enriched in these elements. AVAILABILITY: The CPM software is available upon request from the authors. CONTACT: jstam@stamlab.org; wnoble@u.washington.edu; Charles_Lawrence@brown.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Characterization of pairwise and multiple sequence alignment errors.

Giddy Landan — 2008-07-14T14:47:12-00:00

Gene (3 June 2008)

We characterize pairwise and multiple sequence alignment (MSA) errors by comparing true alignments from simulations of sequence evolution with reconstructed alignments. The vast majority of reconstructed alignments contain many errors. Error rates rapidly increase with sequence divergence, thus, for even intermediate degrees of sequence divergence, more than half of the columns of a reconstructed alignment may be expected to be erroneous. In closely related sequences, most errors consist of the erroneous positioning of a single indel event and their effect is local. As sequences diverge, errors become more complex as a result of the simultaneous mis-reconstruction of many indel events, and the lengths of the affected MSA segments increase dramatically. We found a systematic bias towards underestimation of the number of gaps, which leads to the reconstructed MSA being on average shorter than the true one. Alignment errors are unavoidable even when the evolutionary parameters are known in advance. Correct reconstruction can only be guaranteed when the likelihood of true alignment is uniquely optimal. However, true alignment features are very frequently sub-optimal or co-optimal, with the result that optimal albeit erroneous features are incorporated into the reconstructed MSA. Progressive MSA utilizes a guide-tree in the reconstruction of MSAs. The quality of the guide-tree was found to affect MSA error levels only marginally.

Cell size does not always correspond to genome size: Phylogenetic analysis in geckos questions optimal DNA theories of genome size evolution.

Zuzana Starostová — 2008-07-08T15:32:51-00:00

Zoology (Jena, Germany) (30 June 2008)

At higher taxonomic levels, a significant correlation between genome size (GS) and erythrocyte size (ES) has been reported for many taxa. Under optimal DNA theories, several mechanisms presuming a causative link between GS and ES have been proposed to explain this seemingly general pattern. The correlation between GS and ES has been rarely tested among closely related organisms within an explicit phylogenetic framework. Eyelid geckos (family Eublepharidae) serve as a proper group to conduct such an analysis. We used flow cytometry to measure GS in 15 forms of eublepharids and conducted a phylogenetic reconstruction of GS and ES to test the successiveness of evolutionary shifts in these traits. Most parsimoniously, there were two independent increases and two decreases in GS during the evolution of eublepharids. Nevertheless, changes in GS and ES were not phylogenetically associated in a manner predicted by optimal DNA theories. Our results question the generality of causative bonds between DNA content and cell size and demonstrate that cell size cannot always serve as a proxy of GS. We suggest there is no need to expect a direct causative link between GS and ES to explain the correlation between GS and cell size at higher taxonomic levels. Such a correlation can be explained by simple mechanistic constraints and a combination of the population-genetic model of genome complexity with cell-size-metabolic rate relationship.

Phylogenetic Signal in the Eukaryotic Tree of Life

Michael Sanderson — 2008-07-03T22:12:58-00:00

Science, Vol. 321, No. 5885. (4 July 2008), pp. 121-123.

Molecular sequence data have been sampled from 10% of all species known to science. Although it is not yet feasible to assemble these data into a single phylogenetic tree of life, it is possible to quantify how much phylogenetic signal is present. Analysis of 14,289 phylogenies built from 2.6 million sequences in GenBank suggests that signal is strong in vertebrates and specific groups of nonvertebrate model organisms. Across eukaryotes, however, although phylogenetic evidence is very broadly distributed, for the average species in the database it is equivalent to less than one well-supported gene tree. This analysis shows that a stronger sampling effort aimed at genomic depth, in addition to taxonomic breadth, will be required to build high-resolution phylogenetic trees at this scale. 10.1126/science.1154449

Assessing the Evolutionary Impact of Amino Acid Mutations in the Human Genome

Adam Boyko — 2008-06-30T18:26:56-00:00

PLoS Genet, Vol. 4, No. 5. (30 May 2008), e1000083.

Quantifying the distribution of fitness effects among newly arising mutations in the human genome is key to resolving important debates in medical and evolutionary genetics. Here, we present a method for inferring this distribution using Single Nucleotide Polymorphism (SNP) data from a population with non-stationary demographic history (such as that of modern humans). Application of our method to 47,576 coding SNPs found by direct resequencing of 11,404 protein coding-genes in 35 individuals (20 European Americans and 15 African Americans) allows us to assess the relative contribution of demographic and selective effects to patterning amino acid variation in the human genome. We find evidence of an ancient population expansion in the sample with African ancestry and a relatively recent bottleneck in the sample with European ancestry. After accounting for these demographic effects, we find strong evidence for great variability in the selective effects of new amino acid replacing mutations. In both populations, the patterns of variation are consistent with a leptokurtic distribution of selection coefficients (e.g., gamma or log-normal) peaked near neutrality. Specifically, we predict 27–29% of amino acid changing (nonsynonymous) mutations are neutral or nearly neutral (|s|<0.01%), 30–42% are moderately deleterious (0.01%<|s|<1%), and nearly all the remainder are highly deleterious or lethal (|s|>1%). Our results are consistent with 10–20% of amino acid differences between humans and chimpanzees having been fixed by positive selection with the remainder of differences being neutral or nearly neutral. Our analysis also predicts that many of the alleles identified via whole-genome association mapping may be selectively neutral or (formerly) positively selected, implying that deleterious genetic variation affecting disease phenotype may be missed by this widely used approach for mapping genes underlying complex traits.

EVOLUTION: Building the Tree of Life, Genome by Genome

Elizabeth Pennisi — 2008-06-27T19:25:58-00:00

Science, Vol. 320, No. 5884. (27 June 2008), pp. 1716-1717.

10.1126/science.320.5884.1716

Phylogenetic incongruence in the Drosophila melanogaster species group.

A Wong — 2008-06-27T18:23:27-00:00

Molecular phylogenetics and evolution, Vol. 43, No. 3. (June 2007), pp. 1138-1150.

Drosophila melanogaster and its close relatives are used extensively in comparative biology. Despite the importance of phylogenetic information for such studies, relationships between some melanogaster species group members are unclear due to conflicting phylogenetic signals at different loci. In this study, we use twelve nuclear loci (eleven coding and one non-coding) to assess the degree of phylogenetic incongruence in this model system. We focus on two nodes: (1) the node joining the Drosophila erecta-Drosophila orena, Drosophila melanogaster-Drosophila simulans, and Drosophila yakuba-Drosophila teissieri lineages, and (2) the node joining the lineages leading to the melanogaster, takahashii, and eugracilis subgroups. We find limited evidence for incongruence at the first node; our data, as well as those of several previous studies, strongly support monophyly of a clade consisting of D. erecta-D. orena and D. yakuba-D. teissieri. By contrast, using likelihood based tests of congruence, we find robust evidence for topological incongruence at the second node. Different loci support different relationships among the melanogaster, takahashii, and eugracilis subgroups, and the observed incongruence is not easily attributable to homoplasy, non-equilibrium base composition, or positive selection on a subset of loci. We argue that lineage sorting in the common ancestor of these three subgroups is the most plausible explanation for our observations. Such lineage sorting may lead to biased estimation of tree topology and evolutionary rates, and may confound inferences of positive selection.

A Mixed Branch Length Model of Heterotachy Improves Phylogenetic Accuracy

Bryan Kolaczkowski — 2008-06-26T20:38:53-00:00

Mol Biol Evol, Vol. 25, No. 6. (1 June 2008), pp. 1054-1066.

Evolutionary relationships are typically inferred from molecular sequence data using a statistical model of the evolutionary process. When the model accurately reflects the underlying process, probabilistic phylogenetic methods recover the correct relationships with high accuracy. There is ample evidence, however, that models commonly used today do not adequately reflect real-world evolutionary dynamics. Virtually all contemporary models assume that relatively fast-evolving sites are fast across the entire tree, whereas slower sites always evolve at relatively slower rates. Many molecular sequences, however, exhibit site-specific changes in evolutionary rates, called "heterotachy." Here we examine the accuracy of 2 phylogenetic methods for incorporating heterotachy, the mixed branch length model--which incorporates site-specific rate changes by summing likelihoods over multiple sets of branch lengths on the same tree--and the covarion model, which uses a hidden Markov process to allow sites to switch between variable and invariable as they evolve. Under a variety of simple heterogeneous simulation conditions, the mixed model was dramatically more accurate than homotachous models, which were subject to topological biases as well as biases in branch length estimates. When data were simulated with strong versions of the types of heterotachy observed in real molecular sequences, the mixed branch length model was more accurate than homotachous techniques. Analyses of empirical data sets confirmed that the mixed branch length model can improve phylogenetic accuracy under conditions that cause homotachous models to fail. In contrast, the covarion model did not improve phylogenetic accuracy compared with homotachous models and was sometimes substantially less accurate. We conclude that a mixed branch length approach, although not the solution to all phylogenetic errors, is a valuable strategy for improving the accuracy of inferred trees. 10.1093/molbev/msn042

Fast Evolution of Core Promoters in Primate Genomes

Han Liang — 2008-05-13T16:24:18-00:00

Mol Biol Evol, Vol. 25, No. 6. (1 June 2008), pp. 1239-1244.

Despite much interest in regulatory evolution, how promoters have evolved remains poorly studied, mainly owing to paucity of data on promoter regions. Using a new set of high-quality experimentally determined core promoters of the human genome, we conducted a comparative analysis of 2,492 human and rhesus macaque promoters and their neighboring nearly neutral regions. We found that the core promoters have an average rate of nucleotide substitution substantially higher than that at 4-fold degenerate sites and only slightly lower than that for the assumed neutral controls of neighboring noncoding regions, suggesting that core promoters are subject to very weak selective constraints. Interestingly, we identified 24 core promoters (at false discovery rate = 50%) that have evolved at an accelerated rate compared with the neutral controls, suggesting that they may have undergone positive selection. The inferred positively selected genes show strong bias in molecular function. We also used population genetic approaches to examine the evolution of core promoters in human populations and found evidence of positive selection at some loci. Taken together, our results suggest that positive selection has played a substantial role in the evolution of transcriptional regulation in primates. 10.1093/molbev/msn072

jModelTest: Phylogenetic Model Averaging

David Posada — 2008-06-26T20:29:33-00:00

Mol Biol Evol, Vol. 25, No. 7. (1 July 2008), pp. 1253-1256.

jModelTest is a new program for the statistical selection of models of nucleotide substitution based on "Phyml" (Guindon and Gascuel 2003. A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol. 52:696-704.). It implements 5 different selection strategies, including "hierarchical and dynamical likelihood ratio tests," the "Akaike information criterion," the "Bayesian information criterion," and a "decision-theoretic performance-based" approach. This program also calculates the relative importance and model-averaged estimates of substitution parameters, including a model-averaged estimate of the phylogeny. jModelTest is written in Java and runs under Mac OSX, Windows, and Unix systems with a Java Runtime Environment installed. The program, including documentation, can be freely downloaded from the software section at http://darwin.uvigo.es. 10.1093/molbev/msn083

Morphology and Placental Mammal Phylogeny

Mark Springer — 2008-06-24T20:17:30-00:00

Systematic Biology, Vol. 57, No. 3. (2008), pp. 499-503.

Hemiplasy: A New Term in the Lexicon of Phylogenetics

John Avise — 2008-06-24T20:12:14-00:00

Systematic Biology, Vol. 57, No. 3. (2008), pp. 503-507.

Phylogeny-Aware Gap Placement Prevents Errors in Sequence Alignment and Evolutionary Analysis

Ari Loytynoja — 2008-06-20T03:07:52-00:00

Science, Vol. 320, No. 5883. (20 June 2008), pp. 1632-1635.

Genetic sequence alignment is the basis of many evolutionary and comparative studies, and errors in alignments lead to errors in the interpretation of evolutionary information in genomes. Traditional multiple sequence alignment methods disregard the phylogenetic implications of gap patterns that they create and infer systematically biased alignments with excess deletions and substitutions, too few insertions, and implausible insertion-deletion-event histories. We present a method that prevents these systematic errors by recognizing insertions and deletions as distinct evolutionary events. We show theoretically and practically that this improves the quality of sequence alignments and downstream analyses over a wide range of realistic alignment problems. These results suggest that insertions and sequence turnover are more common than is currently thought and challenge the conventional picture of sequence evolution and mechanisms of functional and structural changes. 10.1126/science.1158395

primetv: A viewer for reconciled trees

Bengt Sennblad — 2007-05-08T17:33:22-00:00

BMC Bioinformatics, Vol. 8 (07 May 2007), 148.

Background Evolutionary processes, such as gene family evolution or parasite-host co-speciation, can often be viewed as a tree evolving inside another tree. Relating two given trees under such a constraint is known as reconciling them. Adequate software tools for generating illustrations of tree reconciliations are instrumental for presenting and communicating results and ideas regarding these phenomena. Available visualization tools have been limited to illustrations of the most parsimonious reconciliation. However, there exists a plethora of biologically relevant non-parsimonious reconciliations. Illustrations of these general reconciliations may not be achieved without manual editing. Results We have developed a new reconciliation viewer, primetv. It is a simple and compact visualization program that is the first automatic tool for illustrating general tree reconciliations. It reads reconciled trees in an extended Newick format and outputs them as tree-within-tree illustrations in a range of graphic formats. Output attributes, such as colors and layout, can easily be adjusted by the user. To enhance the construction of input to primetv, two helper programs, readReconciliation and reconcile, accompany primetv. Detailed examples of all programs' usage are provided in the text. For the casual user a web-service provides a simple user interface to all programs. Conclusion With primetv, the first visualization tool for general reconciliations, illustrations of trees-within-trees are easy to produce. Because it clarifies and accentuates an underlying structure in a reconciled tree, e.g., the impact of a species tree on a gene-family phylogeny, it will enhance scientific presentations as well as pedagogic illustrations in an educational setting. primetv is available at http://prime.sbc.su.se/primetv, both as a standalone command-line tool and as a web service. The software is distributed under the GNU General Public License.

A mobile element based phylogeny of Old World monkeys

Jinchuan Xing — 2008-06-19T21:19:02-00:00

Molecular Phylogenetics and Evolution, Vol. 37, No. 3. (December 2005), pp. 872-880.

SINEs (Short INterspersed Elements) are a class of non-autonomous mobile elements that are <500 bp in length and have no open reading frames. Individual SINE elements are essentially homoplasy free with known ancestral states, making them useful genetic systems for phylogenetic studies. Alu elements are the most successful SINE in primate genomes and have been utilized for resolving primate phylogenetic relationships and human population genetics. However, no Alu based phylogenetic analysis has yet been performed to resolve relationships among Old World monkeys. Using both a computational approach and polymerase chain reaction display methodology, we identified 285 new Alu insertions from sixteen Old World monkey taxa that were informative at various levels of catarrhine phylogeny. We have utilized these elements along with 12 previously reported loci to construct a phylogenetic tree of the selected taxa. Relationships among all major clades are in general agreement with other molecular and morphological data sets but have stronger statistical support.

Moving primate genomics beyond the chimpanzee genome

Morris Goodman — 2008-06-19T21:16:08-00:00

Trends in Genetics, Vol. 21, No. 9. (September 2005), pp. 511-517.

The comparative DNA sequence data that already exist on individual genomic loci depict the phylogenetic relationships of nearly all extant primate genera. Such a phylogenetic representation of the primates, validated by many sequenced primate genomes, and encompassing the full adaptive diversity of the order, is a prerequisite for identifying the genetic basis of humankind, and for testing the proposed human uniqueness of these traits. Some of these traits have been discovered recently, particularly in genes encoding proteins that are important for brain function.

More genes or more taxa? The relative contribution of gene number and taxon number to phylogenetic accuracy.

A Rokas — 2008-06-19T20:48:15-00:00

Molecular biology and evolution, Vol. 22, No. 5. (May 2005), pp. 1337-1344.

The relative contribution of taxon number and gene number to accuracy in phylogenetic inference is a major issue in phylogenetics and of central importance to the choice of experimental strategies for the successful reconstruction of a broad sketch of the tree of life. Maximization of the number of taxa sampled is the strategy favored by most phylogeneticists, although its necessity remains the subject of debate. Vast increases in gene number are now possible due to advances in genomics, but large numbers of genes will be available for only modest numbers of taxa, raising the question of whether such genome-scale phylogenies will be robust to the addition of taxa. To examine the relative benefit of increasing taxon number or gene number to phylogenetic accuracy, we have developed an assay that utilizes the symmetric difference tree distance as a measure of phylogenetic accuracy. We have applied this assay to a genome-scale data matrix containing 106 genes from 14 yeast species. Our results show that increasing taxon number correlates with a slight decrease in phylogenetic accuracy. In contrast, increasing gene number has a significant positive effect on phylogenetic accuracy. Analyses of an additional taxon-rich data matrix from the same yeast clade show that taxon number does not have a significant effect on phylogenetic accuracy. The positive effect of gene number and the lack of effect of taxon number on phylogenetic accuracy are also corroborated by analyses of two data matrices from mammals and angiosperm plants, respectively. We conclude that, for typical data sets, the number of genes utilized may be a more important determinant of phylogenetic accuracy than taxon number.

Molecular phylogeny and divergence times of Malagasy tenrecs: influence of data partitioning and taxon sampling on dating analyses.

Celine Poux — 2008-03-31T18:19:37-00:00

BMC Evolutionary Biology, Vol. 8 (31 March 2008), 102.

BACKGROUND: Malagasy tenrecs belong to the Afrotherian clade of placental mammals and comprise three subfamilies divided in eight genera (Tenrecinae: Tenrec, Echinops, Setifer and Hemicentetes; Oryzorictinae: Oryzorictes, Limnogale and Microgale; Geogalinae:Geogale). The diversity of their morphology and incomplete taxon sampling made it difficult until now to resolve phylogenies based on either morphology or molecular data for this group. Therefore, in order to delineate the evolutionary history of this family, phylogenetic and dating analyses were performed on a four nuclear genes dataset (ADRA2B, AR, GHR and vWF) including all Malagasy tenrec genera. Moreover, the influence of both taxon sampling and data partitioning on the accuracy of the estimated ages were assessed. RESULTS: Within Afrotheria the vast majority of the nodes received a high support, including the grouping of hyrax with sea cow and the monophyly of both Afroinsectivora (Macroscelidea + Afrosoricida) and Afroinsectiphillia (Tubulidentata + Afroinsectivora). Strongly supported relationships were also recovered among all tenrec genera, allowing us to firmly establish the grouping of Geogale with Oryzorictinae, and to confirm the previously hypothesized nesting of Limnogale within the genus Microgale. The timeline of Malagasy tenrec diversification does not reflect a fast adaptive radiation after the arrival on Madagascar, indicating that morphological specializations have appeared over the whole evolutionary history of the family, and not just in a short period after colonization. In our analysis, age estimates at the root of a clade became older with increased taxon sampling of that clade. Moreover an augmentation of data partitions resulted in older age estimates as well, whereas standard deviations increased when more extreme partition schemes were used. CONCLUSION: Our results provide as yet the best resolved gene tree comprising all Malagasy tenrec genera, and may lead to a revision of tenrec taxonomy. A timeframe of tenrec evolution built on the basis of this solid phylogenetic framework showed that morphological specializations of the tenrecs may have been affected by environmental changes caused by climatic and/or subsequent colonization events. Analyses including various taxon sampling and data partitions allow us to point out some possible pitfalls that may lead to biased results in molecular dating; however, further analyses are needed to corroborate these observations.

Uprobe 2008: an online resource for universal overgo hybridization-based probe retrieval and design.

Robert T Sullivan — 2008-06-17T20:55:58-00:00

Nucleic acids research (30 May 2008)

Cross-species sequence comparisons are a prominent method for analyzing genomic DNA and an ever increasing number of species are being selected for whole-genome sequencing. Targeted comparative genomic sequencing is a complementary approach to whole-genome shotgun sequencing and can produce high-quality sequence assemblies of orthologous chromosomal regions of interest from multiple species. Genomic libraries necessary to support targeted mapping and sequencing projects are available for more than 90 vertebrates. An essential step for utilizing these and other genomic libraries for targeted mapping and sequencing is the development of the hybridization-based probes, which are necessary to screen a genomic library of interest. The Uprobe website (http://uprobe.genetics.emory.edu) provides a public online resource for identifying or designing 'universal' overgo-hybridization probes from conserved sequences that can be used to efficiently screen one or more genomic libraries from a designated group of species. Currently, Uprobe provides the ability to search or design probes for use in broad groups of species, including mammals and reptiles, as well as more specific clades, including marsupials, carnivores, rodents and nonhuman primates. In addition, Uprobe has the capability to design custom probes from multiple-species sequence alignments provided by the user, thus providing a general tool for targeted comparative physical mapping.

Genome size diversity in the family Drosophilidae

TR Gregory — 2008-06-04T15:45:33-00:00

Heredity, Vol. aop, No. current.

Flies in the genus Drosophila have been the dominant model organisms in genetics for over a century and, with a dozen complete sequences now available, continue as such in modern comparative genomics. Surprisingly, estimates of genome size for this genus have been relatively sparse, covering less than 2% of species. Here, best practice flow cytometric genome size estimates are reported for both male and female flies from 67 species from six genera in the family Drosophilidae, including 55 species from the genus Drosophila. Direct and phylogenetically corrected correlation analyses indicate that genome size is positively correlated with temperature-controlled duration of development in Drosophila, and there is indication that genome size may be positively related to body size and sperm length in this genus. These findings may provide some explanation for the streamlined genomes found in these insects, and complement recent work demonstrating possible selective constraints on further deletion of noncoding DNA.Heredity advance online publication, 4 June 2008; doi:10.1038/hdy.2008.49.

A diversity profile of the human skin microbiota.

Elizabeth A Grice — 2008-05-28T14:47:11-00:00

Genome research (23 May 2008)

The many layers and structures of the skin serve as elaborate hosts to microbes, including a diversity of commensal and pathogenic bacteria that contribute to both human health and disease. To determine the complexity and identity of the microbes inhabiting the skin, we sequenced bacterial 16S small-subunit ribosomal RNA genes isolated from the inner elbow of five healthy human subjects. This analysis revealed 113 operational taxonomic units (OTUs; "phylotypes") at the level of 97% similarity that belong to six bacterial divisions. To survey all depths of the skin, we sampled using three methods: swab, scrape, and punch biopsy. Proteobacteria dominated the skin microbiota at all depths of sampling. Interpersonal variation is approximately equal to intrapersonal variation when considering bacterial community membership and structure. Finally, we report strong similarities in the complexity and identity of mouse and human skin microbiota. This study of healthy human skin microbiota will serve to direct future research addressing the role of skin microbiota in health and disease, and metagenomic projects addressing the complex physiological interactions between the skin and the microbes that inhabit this environment.

Flying lemurs - the "flying tree shrews"? Molecular cytogenetic evidence for a Scandentia-Dermoptera sister clade

Wenhui Nie — 2008-05-02T11:15:21-00:00

BMC Biology, Vol. 6 (01 May 2008), 18.

Life-history traits drive the evolutionary rates of mammalian coding and noncoding genomic elements

Sergey Nikolaev — 2007-12-12T10:23:23-00:00

Proceedings of the National Academy of Sciences (11 December 2007), 0705658104.

A comprehensive phylogenetic framework is indispensable for investigating the evolution of genomic features in mammals as a whole, and particularly in humans. Using the ENCODE sequence data, we estimated mammalian neutral evolutionary rates and selective pressures acting on conserved coding and noncoding elements. We show that neutral evolutionary rates can be explained by the generation time (GT) hypothesis. Accordingly, primates (especially humans), having longer GTs than other mammals, display slower rates of neutral evolution. The evolution of constrained elements, particularly of nonsynonymous sites, is in agreement with the expectations of the nearly neutral theory of molecular evolution. We show that rates of nonsynonymous substitutions (dN) depend on the population size of a species. The results are robust to the exclusion of hypermutable CpG prone sites. The average rate of evolution in conserved noncoding sequences (CNCs) is 1.7 times higher than in nonsynonymous sites. Despite this, CNCs evolve at similar or even lower rates than nonsynonymous sites in the majority of basal branches of the eutherian tree. This observation could be the result of an overall gradual or, alternatively, lineage-specific relaxation of CNCs. The latter hypothesis was supported by the finding that 3 of the 20 longest CNCs displayed significant relaxation of individual branches. This observation may explain why the evolution of CNCs fits the expectations of the nearly neutral theory less well than the evolution of nonsynonymous sites. 10.1073/pnas.0705658104

Investigations of Oligonucleotide Usage Variance Within and Between Prokaryotes

Jon Bohlin — 2008-04-19T04:19:06-00:00

PLoS Computational Biology, Vol. 4, No. 4. (2008), e1000057.

Oligonucleotide usage in archaeal and bacterial genomes can be linked to a number of properties, including codon usage (trinucleotides), DNA base-stacking energy (dinucleotides), and DNA structural conformation (di- to tetranucleotides). We wanted to assess the statistical information potential of different DNA ‘word-sizes’ and explore how oligonucleotide frequencies differ in coding and non-coding regions. In addition, we used oligonucleotide frequencies to investigate DNA composition and how DNA sequence patterns change within and between prokaryotic organisms. Among the results found was that prokaryotic chromosomes can be described by hexanucleotide frequencies, suggesting that prokaryotic DNA is predominantly short range correlated, i.e., information in prokaryotic genomes is encoded in short oligonucleotides. Oligonucleotide usage varied more within AT-rich and host-associated genomes than in GC-rich and free-living genomes, and this variation was mainly located in non-coding regions. Bias (selectional pressure) in tetranucleotide usage correlated with GC content, and coding regions were more biased than non-coding regions. Non-coding regions were also found to be approximately 5.5% more AT-rich than coding regions, on average, in the 402 chromosomes examined. Pronounced DNA compositional differences were found both within and between AT-rich and GC-rich genomes. GC-rich genomes were more similar and biased in terms of tetranucleotide usage in non-coding regions than AT-rich genomes. The differences found between AT-rich and GC-rich genomes may possibly be attributed to lifestyle, since tetranucleotide usage within host-associated bacteria was, on average, more dissimilar and less biased than free-living archaea and bacteria.

Sequence Context affects the rate of short insertions and deletions in flies and primates

Amos Tanay — 2008-02-21T13:43:45-00:00

Genome Biology, Vol. 9 (21 February 2008), R37.

Widespread Discordance of Gene Trees with Species Tree in Drosophila: Evidence for Incomplete Lineage Sorting

Daniel Pollard — 2008-02-16T07:37:25-00:00

PLoS Genetics, Vol. 2, No. 10. (1 October 2006), e173.

The phylogenetic relationship of the now fully sequenced species Drosophila erecta and D. yakuba with respect to the D. melanogaster species complex has been a subject of controversy. All three possible groupings of the species have been reported in the past, though recent multi-gene studies suggest that D. erecta and D. yakuba are sister species. Using the whole genomes of each of these species as well as the four other fully sequenced species in the subgenus Sophophora, we set out to investigate the placement of D. erecta and D. yakuba in the D. melanogaster species group and to understand the cause of the past incongruence. Though we find that the phylogeny grouping D. erecta and D. yakuba together is the best supported, we also find widespread incongruence in nucleotide and amino acid substitutions, insertions and deletions, and gene trees. The time inferred to span the two key speciation events is short enough that under the coalescent model, the incongruence could be the result of incomplete lineage sorting. Consistent with the lineage-sorting hypothesis, substitutions supporting the same tree were spatially clustered. Support for the different trees was found to be linked to recombination such that adjacent genes support the same tree most often in regions of low recombination and substitutions supporting the same tree are most enriched roughly on the same scale as linkage disequilibrium, also consistent with lineage sorting. The incongruence was found to be statistically significant and robust to model and species choice. No systematic biases were found. We conclude that phylogenetic incongruence in the D. melanogaster species complex is the result, at least in part, of incomplete lineage sorting. Incomplete lineage sorting will likely cause phylogenetic incongruence in many comparative genomics datasets. Methods to infer the correct species tree, the history of every base in the genome, and comparative methods that control for and/or utilize this information will be valuable advancements for the field of comparative genomics.

Darwin's dilemma: the realities of the Cambrian ‘explosion’

Simon Morris — 2008-05-16T20:01:40-00:00

Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 361, No. 1470. (29 June 2006), pp. 1069-1083.

The Cambrian ‘explosion’ is widely regarded as one of the fulcrum points in the history of life, yet its origins and causes remain deeply controversial. New data from the fossil record, especially of Burgess Shale-type Lagerstätten, indicate, however, that the assembly of bodyplans is not only largely a Cambrian phenomenon, but can already be documented in fair detail. This speaks against a much more ancient origin of the metazoans, and current work is doing much to reconcile the apparent discrepancies between the fossil record, including the Ediacaran assemblages of latest Neoproterozoic age and molecular ‘clocks’. Hypotheses to explain the Cambrian ‘explosion’ continue to be generated, but the recurrent confusion of cause and effect suggests that the wrong sort of question is being asked. Here I propose that despite its step-like function this evolutionary event is the inevitable consequence of Earth and biospheric change.

The impact of recombination on nucleotide substitutions in the human genome.

L Duret — 2008-05-15T14:45:42-00:00

PLoS genetics, Vol. 4, No. 5. (May 2008)

Unraveling the evolutionary forces responsible for variations of neutral substitution patterns among taxa or along genomes is a major issue for detecting selection within sequences. Mammalian genomes show large-scale regional variations of GC-content (the isochores), but the substitution processes at the origin of this structure are poorly understood. We analyzed the pattern of neutral substitutions in 1 Gb of primate non-coding regions. We show that the GC-content toward which sequences are evolving is strongly negatively correlated to the distance to telomeres and positively correlated to the rate of crossovers (R2 = 47%). This demonstrates that recombination has a major impact on substitution patterns in human, driving the evolution of GC-content. The evolution of GC-content correlates much more strongly with male than with female crossover rate, which rules out selectionist models for the evolution of isochores. This effect of recombination is most probably a consequence of the neutral process of biased gene conversion (BGC) occurring within recombination hotspots. We show that the predictions of this model fit very well with the observed substitution patterns in the human genome. This model notably explains the positive correlation between substitution rate and recombination rate. Theoretical calculations indicate that variations in population size or density in recombination hotspots can have a very strong impact on the evolution of base composition. Furthermore, recombination hotspots can create strong substitution hotspots. This molecular drive affects both coding and non-coding regions. We therefore conclude that along with mutation, selection and drift, BGC is one of the major factors driving genome evolution. Our results also shed light on variations in the rate of crossover relative to non-crossover events, along chromosomes and according to sex, and also on the conservation of hotspot density between human and chimp.

Physical mapping in large genomes: accelerating anchoring of BAC contigs to genetic maps through in silico analysis.

E Paux — 2008-01-30T17:15:07-00:00

Funct Integr Genomics, Vol. 8, No. 1. (February 2008), pp. 29-32.

Anchored physical maps represent essential frameworks for map-based cloning, comparative genomics studies, and genome sequencing projects. High throughput anchoring can be achieved by polymerase chain reaction (PCR) screening of bacterial artificial chromosome (BAC) library pools with molecular markers. However, for large genomes such as wheat, the development of high dimension pools and the number of reactions that need to be performed can be extremely large making the screening laborious and costly. To improve the cost efficiency of anchoring in such large genomes, we have developed a new software named Elephant (electronic physical map anchoring tool) that combines BAC contig information generated by FingerPrinted Contig with results of BAC library pools screening to identify BAC addresses with a minimal amount of PCR reactions. Elephant was evaluated during the construction of a physical map of chromosome 3B of hexaploid wheat. Results show that a one dimensional pool screening can be sufficient to anchor a BAC contig while reducing the number of PCR by 384-fold thereby demonstrating that Elephant is an efficient and cost-effective tool to support physical mapping in large genomes.

Analysis of Sequence Conservation at Nucleotide Resolution

Saurabh Asthana — 2007-12-31T23:20:24-00:00

PLoS Computational Biology, Vol. 3, No. 12. (1 December 2007), e254.

One of the major goals of comparative genomics is to understand the evolutionary history of each nucleotide in the human genome sequence, and the degree to which it is under selective pressure. Ascertainment of selective constraint at nucleotide resolution is particularly important for predicting the functional significance of human genetic variation and for analyzing the sequence substructure of cis-regulatory sequences and other functional elements. Current methods for analysis of sequence conservation are focused on delineation of conserved regions comprising tens or even hundreds of consecutive nucleotides. We therefore developed a novel computational approach designed specifically for scoring evolutionary conservation at individual base-pair resolution. Our approach estimates the rate at which each nucleotide position is evolving, computes the probability of neutrality given this rate estimate, and summarizes the result in a Sequence CONservation Evaluation (SCONE) score. We computed SCONE scores in a continuous fashion across 1% of the human genome for which high-quality sequence information from up to 23 genomes are available. We show that SCONE scores are clearly correlated with the allele frequency of human polymorphisms in both coding and noncoding regions. We find that the majority of noncoding conserved nucleotides lie outside of longer conserved elements predicted by other conservation analyses, and are experiencing ongoing selection in modern humans as evident from the allele frequency spectrum of human polymorphism. We also applied SCONE to analyze the distribution of conserved nucleotides within functional regions. These regions are markedly enriched in individually conserved positions and short (<15 bp) conserved “chunks.” Our results collectively suggest that the majority of functionally important noncoding conserved positions are highly fragmented and reside outside of canonically defined long conserved noncoding sequences. A small subset of these fragmented positions may be identified with high confidence.

Genomic clocks and evolutionary timescales.

S Blair Hedges — 2008-03-18T19:25:51-00:00

Trends Genet, Vol. 19, No. 4. (April 2003), pp. 200-206.

For decades, molecular clocks have helped to illuminate the evolutionary timescale of life, but now genomic data pose a challenge for time estimation methods. It is unclear how to integrate data from many genes, each potentially evolving under a different model of substitution and at a different rate. Current methods can be grouped by the way the data are handled (genes considered separately or combined into a 'supergene') and the way gene-specific rate models are applied (global versus local clock). There are advantages and disadvantages to each of these approaches, and the optimal method has not yet emerged. Fortunately, time estimates inferred using many genes or proteins have greater precision and appear to be robust to different approaches.

Selection on Major Components of Angiosperm Genomes

Brandon Gaut — 2008-04-25T16:46:21-00:00

Science, Vol. 320, No. 5875. (25 April 2008), pp. 484-486.

Angiosperms are a relatively recent evolutionary innovation, but their genome sizes have diversified remarkably since their origin, at a rate beyond that of most other taxa. Genome size is often correlated with plant growth and ecology, and extremely large genomes may be limited both ecologically and evolutionarily. Yet the relationship between genome size and natural selection remains poorly understood. The manifold cellular and physiological effects of large genomes may be a function of selection on the major components that contribute to genome size, such as transposable elements and gene duplication. To understand the nature of selection on these genomic components, both population-genetic and comparative approaches are needed. 10.1126/science.1153586

Population size and genome size in fishes: a closer look.

TR Gregory — 2008-05-12T18:03:32-00:00

Genome / National Research Council Canada = Génome / Conseil national de recherches Canada, Vol. 51, No. 4. (April 2008), pp. 309-313.

The several thousand-fold range in genome size among animals has remained a subject of active research and debate for more than half a century, but no satisfactory explanation has yet been provided. Many one-dimensional models have been postulated, but so far none has been successful in accounting for observed patterns in genome size diversity. The recent model based on differences in effective population size appeared to gain empirical support with a study of genome size and inferred effective population size in fishes, but there were several questionable aspects of the analysis. First, it was based on an assumption that microsatellite heterozygosity indicates long-term effective population size, whereas in actuality these markers evolve quickly and are sensitive to demographic events. Second, it included both ancient polyploids and non-polyploids, the former of which did not gain their current genome sizes through the accumulation of slightly deleterious mutations as required in the model. Third, the analysis neglected the tremendous influence that Pleistocene glaciation bottlenecks had on heterozygosities in freshwater (and far less so, marine) fishes. In sum, it is apparent that genomes reached their current sizes in most fishes long before contemporary microsatellite heterozygosities were shaped, and that ancient polyploidy rather than the accumulation of mildly deleterious transposon insertions in small populations is the dominant factor that has influenced the large end of the range of genome sizes among fishes.

High-Resolution Mapping and Characterization of Open Chromatin across the Genome.

AP Boyle — 2008-02-06T22:01:36-00:00

Cell, Vol. 132, No. 2. (25 January 2008), pp. 311-322.

Mapping DNase I hypersensitive (HS) sites is an accurate method of identifying the location of genetic regulatory elements, including promoters, enhancers, silencers, insulators, and locus control regions. We employed high-throughput sequencing and whole-genome tiled array strategies to identify DNase I HS sites within human primary CD4(+) T cells. Combining these two technologies, we have created a comprehensive and accurate genome-wide open chromatin map. Surprisingly, only 16%-21% of the identified 94,925 DNase I HS sites are found in promoters or first exons of known genes, but nearly half of the most open sites are in these regions. In conjunction with expression, motif, and chromatin immunoprecipitation data, we find evidence of cell-type-specific characteristics, including the ability to identify transcription start sites and locations of different chromatin marks utilized in these cells. In addition, and unexpectedly, our analyses have uncovered detailed features of nucleosome structure.

Genome size, cell size, and the evolution of enucleated erythrocytes in attenuate salamanders.

Rachel Lockridge Mueller — 2008-05-09T17:02:00-00:00

Zoology (Jena, Germany), Vol. 111, No. 3. (1 May 2008), pp. 218-230.

Within the salamander family Plethodontidae, five different clades have evolved high levels of enucleated red blood cells, which are extremely unusual among non-mammalian vertebrates. In each of these five clades, the salamanders have large genomes and miniaturized or attenuated body forms. Such a correlation suggests that the loss of nuclei in red blood cells may be related, in part, to the interaction between large genome size and small body size, which has been shown to have profound morphological consequences for the nervous and visual systems in plethodontids. Previous work has demonstrated that variation in both the level of enucleated cells and the size of the nuclear genome exists among species of the monophyletic plethodontid genus Batrachoseps. Here, we report extensive intraspecific variation in levels of enucleated red blood cells in 15 species and provide measurements of red blood cell size, nucleus size, and genome size for 13 species of Batrachoseps. We present a new phylogenetic hypothesis for the genus based on 6150bp of mitochondrial DNA sequence data from nine exemplar taxa and use it to examine the relationship between genome size and enucleated red blood cell morphology in a phylogenetic framework. Our analyses demonstrate positive direct correlations between genome size, nucleus size, and both nucleated and enucleated cell sizes within Batrachoseps, although only the relationship between genome size and nucleus size is significant when phylogenetically independent contrasts are used. In light of our results and broader studies of comparative hematology, we propose that high levels of enucleated, variably sized red blood cells in Batrachoseps may have evolved in response to rheological problems associated with the circulation of large red blood cells containing large, bulky nuclei in an attenuate organism.

The evolution of genome size in ants

Neil Tsutsui — 2008-02-27T14:16:14-00:00

BMC Evolutionary Biology, Vol. 8 (26 February 2008), 64.

Using ESTs for phylogenomics: can one accurately infer a phylogenetic tree from a gappy alignment?

Stefanie Hartmann — 2008-03-27T06:01:33-00:00

BMC Evolutionary Biology, Vol. 8 (26 March 2008), 95.

Mapping and sequencing of structural variation from eight human genomes

Jeffrey Kidd — 2008-04-30T19:31:59-00:00

Nature, Vol. 453, No. 7191., pp. 56-64.

Incorporating gaps as phylogenetic characters across eight DNA regions: ramifications for North American Psoraleeae (Leguminosae).

AN Egan — 2008-05-07T18:30:08-00:00

Molecular phylogenetics and evolution, Vol. 46, No. 2. (February 2008), pp. 532-546.

The impact of including insertion/deletion events as phylogenetic characters was explored within North American Psoraleeae (Leguminosae). This comprehensive analysis of the impact of gap character incorporation spanned four different indel coding schemes, gaps coded as missing characters, simple binary characters, multi-state characters, and as a 5th state, across two optimality criteria: maximum parsimony and Bayesian Inference. Two nuclear (ITS and Waxy) and six chloroplast (trnS/G, trnL/F, trnK, matK, trnD/T, and rpoB-trnC) DNA regions were sequenced from 43 species of North American Psoraleeae as the foundation of the study. Our results suggest that gaps can provide a substantial percentage of informative characters and can increase phylogenetic resolution and nodal branch support. Phylogenetic signal within indels was higher in chloroplast regions relative to nuclear regions, demonstrating their inclusion as especially important in chloroplast-based phylogenetic studies. Phylogenetic analysis of generic relationships within Psoraleeae is largely congruent with that proposed by Grimes (1990) with a few exceptions. New World species are supported as a monophyletic group. Our analyses suggest that Otholobium may need to be split into two genera and that Psoralidium is polyphyletic and will require movement of Psoralidium tenuiflorum to Pediomelum.

Confirming the Phylogeny of Mammals by Use of Large Comparative Sequence Datasets.

Arjun Prasad — 2008-05-07T12:34:11-00:00

Molecular biology and evolution (2 May 2008)

The ongoing generation of prodigious amounts of genomic sequence data from myriad vertebrates is providing unparalleled opportunities for establishing definitive phylogenetic relationships among species. The size and complexities of such comparative sequence datasets allow smaller and more-difficult branches to be resolved, but also present unique challenges, including large computational requirements and the negative consequences of systematic biases. To explore these issues and to clarify the phylogenetic relationships among mammals, we have analyzed a large dataset of over 60 megabase pairs (Mb) of high-quality genomic sequence, which we generated from 41 mammals and 3 other vertebrates. All sequences are orthologous to a 1.9-Mb region of the human genome that encompasses the cystic fibrosis transmembrane conductance regulator gene (CFTR). To understand the characteristics and challenges associated with phylogenetic analyses of such a large dataset, we partitioned the sequence data in several ways, and utilized maximum likelihood, maximum parsimony, and neighbor joining algorithms, implemented in parallel on Linux clusters. These studies yielded well-supported phylogenetic trees, largely confirming other recent molecular phylogenetic analyses. Our results provide support for rooting the placental mammal tree between Atlantogenata (Xenarthra and Afrotheria) and Boreoeutheria (Euarchontoglires and Laurasiatheria), illustrate the difficulty in resolving some branches even with large amounts of data (e.g., in the case of Laurasiatheria), and demonstrate the valuable role that very large comparative sequence datasets can play in refining our understanding of the evolutionary relationships of vertebrates.

Computation and Analysis of Genomis Multi-Sequence Alignments.

Mathieu Blanchette — 2007-05-22T23:23:13-00:00

Annu Rev Genomics Hum Genet (9 May 2007)

Multi-sequence alignments of large genomic regions are at the core of many computational genome-annotation approaches aimed at identifying coding regions, RNA genes, regulatory regions, and other functional features. Such alignments also underlie many genome-evolution studies. Here we review recent computational advances in the area of multi-sequence alignment, focusing on methods suitable for aligning whole vertebrate genomes. We introduce the key algorithmic ideas in use today, and identify publicly available resources for computing, accessing, and visualizing genomic alignments. Finally, we describe the latest alignment-based approaches to identify and characterize various types of functional sequences. Key areas of research are identified and directions for future improvements are suggested. Expected final online publication date for the Annual Review of Genomics and Human Genetics Volume 8 is August 30, 2007. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.

Large-scale genomic 2D visualization reveals extensive CG-AT skew correlation in bird genomes

Xuegong Deng — 2007-11-23T14:30:10-00:00

BMC Evolutionary Biology, Vol. 7 (23 November 2007), 234.

Phylogenetic Mixture Models Can Reduce Node-Density Artifacts

Chris Venditti — 2008-04-30T16:16:11-00:00

Systematic Biology, Vol. 57, No. 2. (2008), pp. 286-293.

We investigate the performance of phylogenetic mixture models in reducing a well-known and pervasive artifact of phylogenetic inference known as the node-density effect, comparing them to partitioned analyses of the same data. The node-density effect refers to the tendency for the amount of evolutionary change in longer branches of phylogenies to be underestimated compared to that in regions of the tree where there are more nodes and thus branches are typically shorter. Mixture models allow more than one model of sequence evolution to describe the sites in an alignment without prior knowledge of the evolutionary processes that characterize the data or how they correspond to different sites. If multiple evolutionary patterns are common in sequence evolution, mixture models may be capable of reducing node-density effects by characterizing the evolutionary processes more accurately. In gene-sequence alignments simulated to have heterogeneous patterns of evolution, we find that mixture models can reduce node-density effects to negligible levels or remove them altogether, performing as well as partitioned analyses based on the known simulated patterns. The mixture models achieve this without knowledge of the patterns that generated the data and even in some cases without specifying the full or true model of sequence evolution known to underlie the data. The latter result is especially important in real applications, as the true model of evolution is seldom known. We find the same patterns of results for two real data sets with evidence of complex patterns of sequence evolution: mixture models substantially reduced node-density effects and returned better likelihoods compared to partitioning models specifically fitted to these data. We suggest that the presence of more than one pattern of evolution in the data is a common source of error in phylogenetic inference and that mixture models can often detect these patterns even without prior knowledge of their presence in the data. Routine use of mixture models alongside other approaches to phylogenetic inference may often reveal hidden or unexpected patterns of sequence evolution and can improve phylogenetic inference.

A simulation study of the reliability of recombination detection methods.

C Wiuf — 2008-04-28T15:35:06-00:00

Molecular biology and evolution, Vol. 18, No. 10. (October 2001), pp. 1929-1939.

There exist many methods to detect recombination or mosaic structure in a sample of DNA sequences. But how reliable are they? Four methods were investigated with respect to their power to detect recombination in simulated samples with different amounts of recombination and mutation. In addition, we investigated the impact of the shape of the underlying genealogy on their performances. We found that the methods detected far fewer recombinations than were theoretically possible and that methods based on the principle of incompatibility in general had more power than methods that did not make use of this principle explicitly. This seemed, in particular, to be the case for phylogenies generated under population expansion scenarios which result in long branches at the tips and small deep branches. In addition to the results obtained through simulations, a series of new theoretical results on recombination is presented.

Gene conversion and the evolution of euryarchaeal chaperonins: a maximum likelihood-based method for detecting conflicting phylogenetic signals.

JM Archibald — 2008-04-26T13:18:44-00:00

Journal of molecular evolution, Vol. 55, No. 2. (August 2002), pp. 232-245.

Recombination is well known as a complicating factor in the interpretation of molecular phylogenies. Here we describe a maximum likelihood sliding window method based on a likelihood ratio test for scanning DNA sequence alignments for regions of incongruent phylogenetic signals, such as those influenced by recombination. Using this method, we identify several instances of gene conversion between paralogous chaperonin genes in euryarchaeote Archaea, many of which are not detected by two other widely used methods. In the Thermococcus/Pyrococcus lineage, where a gene duplication producing a and b paralogues predates the divergence of Thermococcus strains KS-1 and KS-8, gene conversion has homogenized portions of the a and b genes in KS-8 since the divergence of these two strains. A region near the 3' end of the a and b paralogues in the methanogen Methanobacterium thermoautotrophicum also appears to have undergone gene conversion. We apply the method to two additional test data sets, the argF gene of Neisseria and a set of actin paralogues in maize, and show that it successfully identifies all the recombinant regions that were previously detected with other methods. Our approach is relatively insensitive to the presence of divergent sequences in the alignment, making it ideal for detecting recombination between both closely and distantly related genes.

Influence Function for Robust Phylogenetic Reconstructions

Avner Bar-Hen — 2008-04-26T12:55:00-00:00

Mol Biol Evol, Vol. 25, No. 5. (1 May 2008), pp. 869-873.

Based on the computation of the influence function, a tool to measure the impact of each piece of sampled data on the statistical inference of a parameter, we propose to analyze the support of the maximum-likelihood (ML) tree for each site. We provide a new tool for filtering data sets (nucleotides, amino acids, and others) in the context of ML phylogenetic reconstructions. Because different sites support different phylogenic topologies in different ways, outlier sites, that is, sites with a very negative influence value, are important: they can drastically change the topology resulting from the statistical inference. Therefore, these outlier sites must be clearly identified and their effects accounted for before drawing biological conclusions from the inferred tree. A matrix containing 158 fungal terminals all belonging to Chytridiomycota, Zygomycota, and Glomeromycota is analyzed. We show that removing the strongest outlier from the analysis strikingly modifies the ML topology, with a loss of as many as 20% of the internal nodes. As a result, estimating the topology on the filtered data set results in a topology with enhanced bootstrap support. From this analysis, the polyphyletic status of the fungal phyla Chytridiomycota and Zygomycota is reinforced, suggesting the necessity of revisiting the systematics of these fungal groups. We show the ability of influence function to produce new evolution hypotheses. 10.1093/molbev/msn030

Analysis of chimpanzee history based on genome sequence alignments.

JL Caswell — 2008-04-25T19:24:02-00:00

PLoS genetics, Vol. 4, No. 4. (April 2008)

Population geneticists often study small numbers of carefully chosen loci, but it has become possible to obtain orders of magnitude for more data from overlaps of genome sequences. Here, we generate tens of millions of base pairs of multiple sequence alignments from combinations of three western chimpanzees, three central chimpanzees, an eastern chimpanzee, a bonobo, a human, an orangutan, and a macaque. Analysis provides a more precise understanding of demographic history than was previously available. We show that bonobos and common chimpanzees were separated approximately 1,290,000 years ago, western and other common chimpanzees approximately 510,000 years ago, and eastern and central chimpanzees at least 50,000 years ago. We infer that the central chimpanzee population size increased by at least a factor of 4 since its separation from western chimpanzees, while the western chimpanzee effective population size decreased. Surprisingly, in about one percent of the genome, the genetic relationships between humans, chimpanzees, and bonobos appear to be different from the species relationships. We used PCR-based resequencing to confirm 11 regions where chimpanzees and bonobos are not most closely related. Study of such loci should provide information about the period of time 5-7 million years ago when the ancestors of humans separated from those of the chimpanzees.