Molecular Biology and Evolution

A Universal Molecular Clock of Protein Folds and its Power in Tracing the Early History of Aerobic Metabolism and Planet Oxygenation.

Publication Date: 2010 Aug 30 PMID: 20805191
Authors: Wang, M. - Jiang, Y. Y. - Kim, K. M. - Qu, G. - Ji, H. F. - Mittenthal, J. E. - Zhang, H. Y. - Caetano-Anolles, G.
Journal: Mol Biol Evol

The standard molecular clock describes a constant rate of molecular evolution and provides a powerful framework for evolutionary timescales. Here we describe the existence and implications of a molecular clock of folds, a universal recurrence in the discovery of new structures in the world of proteins. Using a phylogenomic structural census in hundreds of proteomes we build phylogenies and timelines of domains at fold and fold superfamily levels of structural complexity. These timelines correlate approximately linearly with geological timescales and were here used to date two crucial events in life history, planet oxygenation and organism diversification. We first dissected the structures and functions of enzymes in simulated metabolic networks. The placement of anaerobic and aerobic enzymes in the timeline revealed that aerobic metabolism emerged approximately 2.9 billion years (Ga) ago and expanded during a period of approximately 400 million years, reaching what is known as the Great Oxidation Event. During this period, enzymes recruited old and new folds for oxygen-mediated enzymatic activities. Remarkably, the first fold lost by a superkingdom disappeared in Archaea 2.6 Ga ago, within the span of oxygen rise, suggesting oxygen also triggered diversification of life. The implications of a molecular clock of folds are many and important for the neutral theory of molecular evolution and for understanding the growth and diversity of the protein world. The clock also extends the standard concept that was specific to molecules and their timescales and turns it into a universal timescale-generating tool.

post to: CiteULike

Extreme reconfiguration of plastid genomes in the angiosperm family Geraniaceae: rearrangements, repeats, and codon usage.

Publication Date: 2010 Aug 30 PMID: 20805190
Authors: Guisinger, M. M. - Kuehl, J. V. - Boore, J. L. - Jansen, R. K.
Journal: Mol Biol Evol

Geraniaceae plastid genomes (plastomes) have experienced a remarkable number of genomic changes. The plastomes of Erodium texanum, Geranium palmatum, and Monsonia speciosa were sequenced and compared to other rosids and the previously published Pelargonium hortorum plastome. Geraniaceae plastomes were found to be highly variable in size, gene content and order, repetitive DNA, and codon usage. Several unique plastome rearrangements include the disruption of two highly conserved operons (S10 and rps2-atpA), and the inverted repeat region (IR) in M. speciosa does not contain all genes in the rRNA operon. The sequence of M. speciosa is unusually small (128,787 bp); among angiosperm plastomes sequenced to date, only those of nonphotosynthetic species and those that have lost one IR copy are smaller. In contrast, the plastome of P. hortorum is the largest, at 217,942 bp. These genomes have experienced numerous gene and intron losses and partial and complete gene duplications. Some of the losses are shared throughout the family (e.g., trnT-GGU and the introns of rps16 and rpl16); however, other losses are homoplasious (e.g., trnG-UCC intron in G. palmatum and M. speciosa). IR length is also highly variable. The IR in P. hortorum was previously shown to be greatly expanded to 76 kb, and the IR is lost in E. texanum and reduced in G. palmatum (11 kb) and M. speciosa (7 kb). Geraniaceae plastomes contain a high frequency of large repeats (>100 bp) relative to other rosids. Within each plastome, repeats are often located at rearrangement endpoints, and many repeats shared among the four Geraniaceae flank rearrangement endpoints. GC content is elevated in the genomes and also in coding regions relative to other rosids. Codon usage per amino acid and GC content at third position sites are significantly different for Geraniaceae protein-coding sequences relative to other rosids. Our findings suggest that relaxed selection and/or mutational biases lead to increased GC content and this in turn altered codon usage. We propose that increases in genomic rearrangements, repetitive DNA, nucleotide substitutions, and GC content may be caused by relaxed selection resulting from improper DNA repair.

post to: CiteULike

MicroRNA Networks Alter to Conform to Transcription Factor Networks Adding Redundancy and Reducing the Repertoire of Target Genes for Coordinated Regulation.

Publication Date: 2010 Aug 30 PMID: 20805189
Authors: Iwama, H. - Murao, K. - Imachi, H. - Ishida, T.
Journal: Mol Biol Evol

Transcription factors (TFs) and microRNAs (miRNAs) comprise two major layers of gene regulatory networks (GRNs). TFs and miRNAs function coordinately, but they have distinct molecular mechanisms and evolutionary backgrounds. Therefore, we aimed to systematically reveal the difference in contribution between TF and miRNA networks to the evolution of their coordinated regulations by focusing on composite feedforward circuits (cFFCs), that each comprises a TF and an miRNA. We compiled 124736 human-mouse conserved TF regulatory connections and 34298 conserved miRNA regulatory connections into two distinct connection matrices. To differentially assess the contributions to cFFC formation of TFs and miRNAs, we randomized one matrix and kept the other unchanged, and subsequently examined the number of cFFCs, the number of cFFC-targeted genes, and the redundancy formed by cFFCs in comparison with those of the real GRNs. Since the matrices represent selectively constrained networks, if selection has been operating on the networks for or against cFFC formation, the values of cFFC network properties would deviate significantly from the expectation of the randomized networks. As the cFFC includes both TF and miRNA connections, the partial randomizations indicate the extent of influence of selection on cFFC formation differentially between TF and miRNA networks. Thus, we adopted the deviation of each cFFC network property value as a measure to estimate the extent of influence of selection on cFFCs and to compare the contribution between TF and miRNA networks. We found that miRNA regulatory networks changed their configuration such that they conformed to the stable TF regulatory networks with an increased circuit redundancy and a marked reduction in the repertoire of cFFC-targeted genes. We also revealed that this redundancy-adding role is preferentially attributable to miRNA network alterations. The results indicate that the redundancy-adding role might serve as a niche for many miRNA connections to survive, avoiding conflicts with the stable TF regulatory networks.

post to: CiteULike

Comparative proteomics uncovers the signature of natural selection acting on the ejaculate proteomes of two cricket species isolated by postmating, prezygotic phenotypes.

Publication Date: 2010 Aug 30 PMID: 20805188
Authors: Marshall, J. L. - Huestis, D. L. - Garcia, C. - Hiromasa, Y. - Wheeler, S. - Noh, S. - Tomich, J. M. - Howard, D. J.
Journal: Mol Biol Evol

Two of the most well-supported patterns to have emerged over the past two decades of research in evolutionary biology are the occurrence of divergent natural selection acting on many male and female reproductive tract proteins and the importance of postmating, prezygotic phenotypes in reproductively isolating closely related species. Although these patterns appear to be common across a wide variety of taxa, the link between them remains poorly documented. Here, we utilize comparative proteomic techniques to determine whether or not there is evidence for natural selection acting on the ejaculate proteomes of two cricket species (Allonemobius fasciatus and A. socius) which are reproductively isolated primarily by postmating, prezygotic phenotypes. In addressing this question, we compare the degree of within-species polymorphism and between-species divergence between the ejaculate and thorax proteomes of these two species. We found that the ejaculate proteomes are both less polymorphic and more divergent than the thorax proteomes. Additionally, we assessed patterns of nucleotide variation for two species-specific ejaculate proteins and found evidence for both reduced levels of variation within species and positive selection driving divergence between species. In contrast, non-species-specific proteins exhibited higher levels of within species nucleotide variation and no signatures of positive selection. Nucleotide and putative functional data for the two species-specific proteins, along with data for a third protein (Ejaculate Serine Protease), suggest that all three of these genes are candidate speciation genes in need of further study. Overall, these patterns of proteome and nucleotide divergence provide support for the hypothesis that there is a causative link between selection-driven divergence of male ejaculate proteins and the evolution of postmating, prezygotic barriers to gene flow within Allonemobius.

post to: CiteULike

Evolutionary history of chimpanzees inferred from complete mitochondrial genomes.

Publication Date: 2010 Aug 28 PMID: 20802239
Authors: Bjork, A. - Liu, W. - Wertheim, J. O. - Hahn, B. H. - Worobey, M.
Journal: Mol Biol Evol

Investigations into the evolutionary history of the common chimpanzee, Pan troglodytes, have produced inconsistent results, due to differences in the types of molecular data considered, the model assumptions employed, and the quantity and geographical range of samples used. We amplified and sequenced 24 complete P. troglodytes mitochondrial genomes from fecal samples collected at multiple study sites throughout sub-Saharan Africa. Using a 'relaxed molecular clock,' fossil calibrations, and 12 additional complete primate mitochondrial genomes, we analyzed the pattern and timing of primate diversification in a Bayesian framework. Our results support the recognition of four chimpanzee subspecies. Within P. troglodytes, we report a mean (95% highest posterior density (HPD)) time since most recent common ancestor (tMRCA) of 1.026 (0.811-1.263) MYA for the four proposed subspecies, with two major lineages. One of these lineages (tMRCA = 0.510 [0.387-0.650] MYA) contains P. t. verus (tMRCA = 0.155 [0.101-0.213] MYA) and P. t. ellioti (formerly P. t. vellerosus; tMRCA = 0.157 [0.102-0.215] MYA), both of which are monophyletic. The other major lineage contains P. t. schweinfurthii (tMRCA = 0.111 [0.077-0.146] MYA), a monophyletic clade nested within the P. t. troglodytes lineage (tMRCA = 0.380 [0.296-0.476] MYA). We utilized two analysis techniques that may be of widespread interest. First, we implemented a Yule speciation prior across the entire primate tree with separate coalescent priors on each of the chimpanzee subspecies. The validity of this approach was confirmed by estimates based on more traditional techniques. We also suggest that accurate tMRCA estimates from large, computationally difficult sequence alignments may be obtained by implementing our novel method of bootstrapping smaller, randomly sub-sampled alignments.

post to: CiteULike

Population Genetic Analysis of the Uncoupling Proteins Supports a Role for UCP3 in Human Cold Resistance.

Publication Date: 2010 Aug 28 PMID: 20802238
Authors: Hancock, A. M. - Clark, V. J. - Qian, Y. - Di Rienzo, A.
Journal: Mol Biol Evol

Production of heat via non-shivering thermogenesis (NST) is critical for temperature homeostasis in mammals. Uncoupling protein UCP1 plays a central role in NST by uncoupling the proton gradients produced in the inner membranes of mitochondria to produce heat; however, the extent to which UCP1 homologues, UCP2 and UCP3, are involved in NST is the subject of an ongoing debate. We used an evolutionary approach to test the hypotheses that variants that are associated with increased expression of these genes (UCP1 -3826A, UCP2 -866A and UCP3 -55T) show evidence of adaptation with winter climate. To that end, we calculated correlations between allele frequencies and winter climate variables for these SNPs, which we genotyped in a panel of 52 worldwide populations. We found significant correlations with winter climate for UCP1 -3826 G/A and UCP3 -55 C/T. Further, by analyzing previously published genotype data for these SNPs we found that the peak of the correlation for the UCP1 region occurred at the disease associated -3826A/G variant and that the UCP3 region has a striking signal overall, with several individual SNPs showing interesting patterns, including the -55 C/T variant. Re-sequencing of the regions in a set of 3 diverse population samples helped to clarify the signals that we found with the genotype data. At UCP1, the re-sequencing data revealed modest evidence that the haplotype carrying the -3826A variant was driven to high frequency by selection. In the UCP3 region, combining results from the climate analysis and re-sequencing survey suggests a more complex model in which variants on multiple haplotypes may independently be correlated with temperature. This is further supported by an excess of intermediate frequency variants in the UCP3 region in the Han Chinese population. Taken together, our results suggest that adaptation to climate influenced the global distribution of allele frequencies in UCP1 and UCP3, and provide an independent source of evidence for a role in cold resistance for UCP3.

post to: CiteULike

Combining comparative sequence and genomic data to ascertain phylogenetic relationships and explore the evolution of the large GDSL-lipase family in land-plants.

Publication Date: 2010 Aug 26 PMID: 20801908
Authors: Volokita, M. - Rosilio-Brami, T. - Rivkin, N. - Zik, M.
Journal: Mol Biol Evol

The GDSL-lipase gene family is a very large sub-family within the super gene family of SGNH esterases, defined by the distinct GDSL amino acid motif and several highly conserved domains. Plants retain a large number of GDSL-lipases indicating that they have acquired important functions. Yet, in planta functions have been demonstrated for only a few GDSL-lipases from diverse species. Considering that orthologs often retain equivalent functions, we determined the phylogentic relationships between GDSL-lipases from genome-sequenced species representing bryophytes, gymnosperms, monocots and eudicots. An unrooted phylogenetic tree was constructed from the amino acid sequences of 604 GDSL-lipases from seven species. The topology of the tree depicts two major and one minor sub-family. This division is also supported by the unique gene structure of each sub-family. Since GDSL-lipase genes of all species are present in each of the three sub-families, we conclude that the last common ancestor of the land plants already possessed at least one ancestral GDSL-lipase gene of each sub-family. Combined gene structure and synteny analyses revealed events of segmental duplications, gene transposition, and gene degeneration in the evolution of the GDSL-lipase gene family. Furthermore, these analyses showed that independent events of intron gain and loss also contributed to the extant repertoire of the GDSL-lipase gene family. Our findings suggest that underlying many of the intron losses was a spliceosomal-mediated mechanism followed by gene conversion. Sorting the phylogentic relationships among the members of the GDSL-lipase gene family, as depicted by the tree and supported by synteny analyses, provides a framework for extrapolation of demonstrated functional data to GDSL-lipases whose function is yet unknown. Furthermore, function(s) associated with specific lineage(s)-enriched branches may reveal correlations between acquired and/or lost functions and speciation.

post to: CiteULike

Choosing among partition models in Bayesian phylogenetics.

Publication Date: 2010 Aug 27 PMID: 20801907
Authors: Fan, Y. - Wu, R. - Chen, M. H. - Kuo, L. - Lewis, P. O.
Journal: Mol Biol Evol

Bayesian phylogenetic analyses often depend on Bayes factors (BF) to determine the optimal way to partition the data. The marginal likelihoods used to compute Bayes factors, in turn, are most commonly estimated using the harmonic mean (HM) method, which has been shown to be inaccurate. We describe a new, more accurate method for estimating the marginal likelihood of a model and compare it to the HM method on both simulated and empirical data. The new method generalizes our previously-described stepping-stone (SS) approach by making use of a reference distribution parameterized using samples from the posterior distribution. This avoids one challenging aspect of the original SS method, namely the need to sample from distributions that are close (in the Kullback-Leibler sense) to the prior. We specifically address the choice of partition models, and find that using the HM method can lead to a strong preference for an overpartitioned model. In contrast to the HM method and the original SS method, we show using simulated data that the generalized SS method is strikingly more precise (repeatable BF values of the same data and partition model) and yields BF values that are much more reasonable than those produced by the HM method. Comparisons of HM and generalized SS methods on an empirical data set demonstrate that the generalized SS method tends to choose simpler partition schemes that are more in line with expectation based on inferred patterns of molecular evolution. The generalized SS method shares with thermodynamic integration the need to sample from a series of distributions in addition to the posterior. Such dedicated path-based Markov chain Monte Carlo (MCMC) analyses appear to be a cost of estimating marginal likelihoods accurately.

post to: CiteULike

A Comprehensive Functional Analysis of Ancestral Human Signal Peptides.

Publication Date: 2010 Aug 26 PMID: 20798139
Authors: Gralle, M. - Paabo, S.
Journal: Mol Biol Evol

With the sequencing of the Neandertal genome, it has become possible to identify amino acid substitutions that occurred on the human lineage since its separation from the Neandertal lineage. Conceptually, it will therefore be possible to functionally analyze all such amino acid substitutions in the future. Here we analyze the function of substitutions that occurred during recent human evolution in N-terminal signal peptides. We develop a high-throughput flow cytometry-based assay to analyze signal peptide efficiency as the ratio of surface to total reporter protein per live cell. Such ratios differed significantly among signal peptides derived from different human genes. However, no modern human signal peptide differed significantly from its ancestral counterpart, an observation compatible with the predictions of the neutral theory of molecular evolution.

post to: CiteULike

Elevated evolutionary rate in genes with homopolymeric amino acid repeats constituting non-disordered structure.

Publication Date: 2010 Aug 26 PMID: 20798138
Authors: Gojobori, J. - Ueda, S.
Journal: Mol Biol Evol

Homopolymeric amino acid repeats are tandem repeats of single amino acids. About 650 genes are known to have repeats of this kind comprising seven residues or more in the human genome. According to the evolutionary conservativeness, we classified the repeats into three categories: those whose length is conserved among mammals (CM), those whose length differs among nonprimate mammals but is conserved among primates (CP), and those whose length differs among primates (VP). The frequency of each repeat, especially Ala, Leu, Pro, and Glu repeats, varies greatly in each category. The three-dimensional structure of homopolymeric amino acid repeats is considered to be intrinsically disordered. As expected, a large proportion of the repeats had a disordered structure, and nearly half of the repeats were predicted as completely disordered. However, a number of the repeats predicted to have non-disordered structure: 13 and 25 % of the repeats for categories CM and VP, respectively. Comparison of the substitution rates showed a higher Ka/Ks ratio for the genes with not disordered repeats than the genes with disordered repeats. These results indicate that amino acid substitution rates have been elevated in the genes with non-disordered repeats.

post to: CiteULike

Functional compensation of primary and secondary metabolites by duplicate genes in Arabidopsis thaliana.

Publication Date: 2010 Aug 24 PMID: 20736450
Authors: Hanada, K. - Sawada, Y. - Kuromori, T. - Klausnitzer, R. - Saito, K. - Toyoda, T. - Shinozaki, K. - Li, W. H. - Hirai, M. Y.
Journal: Mol Biol Evol

It is well known that knocking out a gene in an organism often causes no phenotypic effect. One possible explanation is the existence of duplicate genes; that is, the effect of knocking out a gene is compensated by a duplicate copy. Another explanation is the existence of alternative pathways. In terms of metabolic products, the relative roles of the two mechanisms have been extensively studied in yeast, but not in any multicellular organisms. Here, to address the functional compensation of metabolic products by duplicate genes, we quantified 35 metabolic products from 1,976 genes in knock-out mutants of Arabidopsis thaliana by a high-throughput LC-MS analysis. We found that knocking out either a singleton gene or a duplicate gene with distant paralogs in the genome tends to induce stronger metabolic effects than knocking out a duplicate gene with a close paralog in the genome, indicating that only duplicate genes with close paralogs play a significant role in functional compensation for metabolic products in A. thaliana. To extend the analysis, we examined metabolic products with either high or low connectivity in a metabolic network. We found that the compensatory role of duplicate genes is less important when the metabolite has a high connectivity, indicating that functional compensation by alternative pathways is common in the case of high connectivity. In conclusion, recently duplicated genes play an important role in the compensation of metabolic products only when the number of alternative pathways is small.

post to: CiteULike

Comparative vertebrate evolutionary analyses of type I collagen: potential of COL1a1 gene structure and intron variation for common bone-related diseases.

Publication Date: 2010 Aug 19 PMID: 20724381
Authors: Stover, D. A. - Verrelli, B. C.
Journal: Mol Biol Evol

Collagen type I alpha 1 (COL1a1), which encodes the primary subunit of type I collagen, the main structural and most abundant protein in vertebrates, harbors hundreds of mutations linked to human diseases like osteoporosis and osteogenesis imperfecta. Previous studies have attempted to predict the phenotypic severity associated with type I collagen mutations, yet an evolutionary analysis that compares historical and recent selective pressures, including across non-coding regions, has never been conducted. Here, we use a comparative genomic and species evolutionary analysis representing approximately 450 My of vertebrate history to investigate functional constraints associated with both exons and introns of the >17-kb COL1a1 gene. We find that although the COL1a1 amino acid sequence is highly conserved, there are both spatial and temporal signatures of selective constraint across protein domains. Further, sites of high evolutionary constraint significantly correlate with the location of disease-associated mutations, the latter of which also cluster with respect to specific severity classes typically categorized in clinical studies. Finally, we find that COL1a1 introns are significantly short in length with high GC-content, patterns that are shared across highly-diverged vertebrates, and which may be a signature of strong stabilizing selection for high COL1a1 gene expression. In conclusion, although previous studies focused on COL1a1 coding regions, the current results implicate introns as areas of high selective constraint and targets of bone-related phenotypic variation. From a broader perspective, our comparative evolutionary approach provides further resolution to models predicting mutations associated with bone-related function and disease severity.

post to: CiteULike

Conservation and evolution in and among SRF- and MEF2-type MADS domains and their binding sites.

Publication Date: 2010 Aug 19 PMID: 20724380
Authors: Wu, W. - Huang, X. - Cheng, J. - Li, Z. - de Folter, S. - Huang, Z. - Jiang, X. - Pang, H. - Tao, S.
Journal: Mol Biol Evol

Serum response factor (SRF) and myocyte enhancer factor 2 (MEF2) represent two types of members of the MADS-box transcription factor family present in animals and fungi. Each type has distinct biological functions, which are reflected by the distinct specificities of the proteins bound to their cognate DNA-binding sites and activated by their respective cofactors. However, little is known about the evolution of MADS domains and their DNA binding sites. Here, we report on the conservation and evolution of the two types of MADS domains with their cognate DNA binding sites by using phylogenetic analyses. First, there are great similarities between the two types of proteins with amino acid positions highly conserved, which are critical for binding to the DNA sequence and for the maintenance of the three-dimensional structure. Second, in contrast to MEF2-type MADS domains, distinct conserved residues are present at some positions in SRF-type MADS domains, determining specificity and the configuration of the MADS domain bound to DNA sequences. Furthermore, the ancestor sequence of SRF- and MEF2-type MADS domains is more similar to MEF2-type MADS domains than to SRF-type MADS domains. In the case of DNA binding sites, the MEF2 site has a T-rich core in one DNA sequence and an A-rich core in the reverse sequence as compared to the SRF site, no matter whether where either A or T is present in the two complementary sequences. In addition, comparing SRF sites in the human and the mouse genomes reveals that the evolution rate of CArG-boxes is faster in mouse than in human. Moreover, interestingly, a CArG-like sequence, which is probably functionless, could potentially mutate to a functional CArG-box that can be bound by SRF and vice versa. Together, these results significantly improve our knowledge on the conservation and evolution of the MADS domains and their binding sites to date and provide new insights to investigate the MADS family, which is not only on evolution of MADS factors but also on evolution of their binding sites and even on coevolution of MADS factors with their binding sites.

post to: CiteULike

Phylogenetic substitution models for detecting heterotachy during plastid evolution.

Publication Date: 2010 Aug 19 PMID: 20724379
Authors: Whelan, S. - Blackburne, B. P. - Spencer, M.
Journal: Mol Biol Evol

There is widespread evidence of lineage-specific rate variation, known as heterotachy, during protein evolution. Changes in the structural and functional constraints acting on a protein can lead to heterotachy, and it is plausible that such changes, known as covarion shifts, may affect many amino acids at once. Several previous attempts to model heterotachy have used covarion models, where the sequence undergoes covarion drift, whereby each site may switch independently among a set of discrete classes having different substitution rates. However, such independent switching may not capture biologically important events where the selective forces acting on a protein affect many sites at once. We describe a new class of models that allow the rates of substitution and switching to vary among branches of a phylogenetic tree. Such models are better able to handle covarion shifts. We apply these models to a set of genes occurring in non-photosynthetic bacteria, cyanobacteria, and the plastids of green and red algae. We find that 4/5 genes show evidence of some form of rate switching and that 3/5 genes show evidence that the relative switching rate differs among taxonomic groups. We conclude that covarion shifts may be frequent during the deep evolution of plastid genes and that our methodology may provide a powerful new tool for investigating such shifts in other systems.

post to: CiteULike

NUMTs in the sponge genome reveal conserved transposition mechanisms in metazoans.

Publication Date: 2010 Aug 18 PMID: 20720154
Authors: Erpenbeck, D. - Voigt, O. - Adamski, M. - Woodcroft, B. J. - Hooper, J. N. - Worheide, G. - Degnan, B. M.
Journal: Mol Biol Evol

The transposition of parts of the mitochondrial genetic material into the nuclear genome (NUMTs) occurs in a wide range of eukaryotes. Here we show that NUMTs exist for nearly all regions of the mitochondrial genome in the demosponge Amphimedon queenslandica, a representative of the oldest phyletic lineage of animals. Since the sponge NUMTs are small and non-coding, and transposed via a DNA intermediate, as in eumetazoans, we infer that the transpositonal processes underlying NUMT formation in contemporary animals existed in their most recent common ancestor. In contrast to most bilaterians, Amphimedon NUMTs are inserted into regions of high gene density. Given the common features of metazoan NUMTs, the reduction in animal mitochondrial genome sizes relative to other eukaryotes may be the product of the mitochondrial DNA transposition mechanisms that evolved along the metazoan stem.

post to: CiteULike

Recent expansion of a new Ingi-related clade of Vingi non-LTR retrotransposons in hedgehogs.

Publication Date: 2010 Aug 17 PMID: 20716533
Authors: Kojima, K. K. - Kapitonov, V. V. - Jurka, J.
Journal: Mol Biol Evol

Autonomous non-long terminal repeat (non-LTR) retrotransposons and their repetitive remnants are ubiquitous components of mammalian genomes. Recently, we identified non-LTR retrotransposon families, Ingi-1_AAl and Ingi-1_EE, in two hedgehog genomes. Here we rename them to Vingi-1_AAl and Vingi-1_EE and report a new clade "Vingi", which is a sister clade of Ingi that lacks the ribonuclease H domain. In the European hedgehog genome, there are 11 non-autonomous families of elements derived from Vingi-1_EE by internal deletions. No retrotransposons related to Vingi elements were found in any of the remaining 33 mammalian genomes nearly completely sequenced to date, but we identified several new families of Vingi and Ingi retrotransposons outside mammals. Our data suggest the horizontal transfer of Vingi elements to hedgehog, although the vertical transfer cannot be ruled out. The compact structure and trans-mobilization of non-autonomous derivatives of Vingi can make them useful for in vivo retrotransposition assay system.

post to: CiteULike

Alu monomer revisited: Recent generation of Alu monomers.

Publication Date: 2010 Aug 16 PMID: 20713470
Authors: Kojima, K. K.
Journal: Mol Biol Evol

Alu is a predominant short interspersed element (SINE) family in the human genome and consists of two monomer units connected by an A-rich linker. At present, dimeric Alu elements are active in humans, but Alu monomers are present as fossilized sequences. A comparative genome analysis of human and chimpanzee genomes revealed 8 recent insertions of Alu monomers. One of them was a retroposed product of another Alu monomer with 3' transduction. Further analysis of 1404 loci of the Alu monomer in the human genome revealed that some Alu monomers were recently generated by recombination between the internal and 3' A-rich tracts inside of dimeric Alu elements. The data show that Alu monomers were generated by (1) retroposition of other Alu monomers, and (2) recombination between 2 A-rich tracts.

post to: CiteULike

Contrasting evolutionary patterns of the Rp1 resistance gene family in different species of Poaceae.

Publication Date: 2010 Aug 16 PMID: 20713469
Authors: Luo, S. - Peng, J. - Li, K. - Wang, M. - Kuang, H.
Journal: Mol Biol Evol

Disease resistance genes (R-genes) in plants show complex evolutionary patterns. We investigated the evolution of the Rp1 R-gene family in Poaceae, and 409 Rp1 fragments were sequenced from 21 species. Our data showed that the common ancestor of Poaceae had two Rp1 loci, but the number of Rp1 locus in extant species varies from one to five. Some wheat and Zea genotypes have dozens of Rp1 homologues, in striking contrast to one or two copies in Brachypodium distachyon. The large number of diverse Rp1 homologues in Zea was the results of duplications followed by extensive sequence exchanges among paralogues, and all genes in maize have evolved in a pattern of Type I R-genes. The high frequency of sequence exchanges did not cause concerted evolution in Zea species but concerted evolution was obvious between Rp1 homologues from genera Zea and Sorghum. Differentiation of Type I and Type II Rp1 homologues was observed in Oryza species, likely occurred in their common ancestor. One member (Type II R-gene) in the Oryza Rp1 cluster did not change sequences with its paralogues, while the other paralogues (Type I R-genes) had frequent sequence exchanges. The functional Pi37 resistance gene in rice was generated through an unequal crossover between two neighboring paralogues followed by four point mutations. The Rp1 homologues in wheat and barley were most divergent, probably due to lack of sequence exchanges among them. Our results shed more light on R-gene evolution, particularly on the differentiation of Type I and Type II R-genes.

post to: CiteULike

Large-scale mtDNA screening reveals a surprising matrilineal complexity in East Asia and its implications to the peopling of the region.

Publication Date: 2010 Aug 16 PMID: 20713468
Authors: Kong, Q. P. - Sun, C. - Wang, H. W. - Zhao, M. - Wang, W. Z. - Zhong, L. - Hao, X. D. - Pan, H. - Wang, S. Y. - Cheng, Y. T. - Zhu, C. L. - Wu, S. F. - Liu, L. N. - Jin, J. Q. - Yao, Y. G. - Zhang, Y. P.
Journal: Mol Biol Evol

In order to achieve a thorough coverage of the basal lineages in the Chinese matrilineal pool, we have sequenced the mitochondrial DNA (mtDNA) control region and partial coding-region segments of 6,093 mtDNAs sampled from 84 populations across China. By comparing with the available complete mtDNA sequences, 194 of those mtDNAs could not be firmly assigned into the available haplogroups. Completely sequencing 51 representatives selected from these unclassified mtDNAs identified a number of novel lineages, including five novel basal haplogroups that directly emanate from the Eurasian founder nodes (M and N). No matrilineal contribution from the archaic hominid was observed. Subsequent analyses suggested that these newly identified basal lineages likely represent the genetic relics of modern humans initially peopling East Asia, instead of being the results of gene flow from the neighboring regions. The observation that most of the newly recognized mtDNA lineages have already differentiated and show the highest genetic diversity in southern China provided additional evidence in support of the Southern-Route peopling hypothesis of East Asians. Specifically, the enrichment of most of the basal lineages in southern China and their rather ancient ages in Late Pleistocene further suggested that this region was likely the genetic reservoir of modern humans after they entered East Asia.

post to: CiteULike

A new test for detecting recent positive selection that is free from the confounding impacts of demography.

Publication Date: 2010 Aug 13 PMID: 20709734
Authors: Li, H.
Journal: Mol Biol Evol

It has been a long-standing interest in evolutionary biology to search for the traces of recent positive Darwinian selection in organisms. However, such efforts have been severely hindered by the confounding signatures of demography. As a consequence neutrality tests often lead to false inference of positive selection since they detect the deviation from the standard neutral model. Here, using the maximum frequency of derived mutations (MFDM) to examine the unbalanceness of the tree of a locus, I propose a statistical test that is analytically free from the confounding effects of varying population size and has a high statistical power (up to 90.5%) to detect recent positive selection. When compared with five well-known neutrality tests for detecting selection (i.e., Tajima's D-test, Fu & Li's D-test, Fay & Wu's H-test, the E-test and the joint DH test), the MFDM test is indeed the only one free from the confounding impacts of bottlenecks and size expansions. Simulations based on wide-range parameters demonstrated that the MFDM test is robust to background selection, population subdivision and admixture (including hidden population structure). Moreover, when two high-frequency mutations are introduced, the MFDM test is robust to the misinference of derived and ancestral variants of segregating sites due to multiple hits. Finally, the sensitivity of the MFDM test in detecting balancing selection is also discussed. In summary, it is demonstrated that summary statistics based on tree topology can be used to detect selection, and this work provides a reliable method that can distinguish selection from demography even when DNA polymorphism data from only one locus is available.

post to: CiteULike

Comparative analysis of metabolic networks provides insight into the evolution of plant pathogenic and non-pathogenic lifestyles in Pseudomonas.

Publication Date: 2010 Aug 13 PMID: 20709733
Authors: Mithani, A. - Hein, J. - Preston, G. M.
Journal: Mol Biol Evol

Plant pathogenic pseudomonads such as Pseudomonas syringae colonize plant surfaces and tissues and have been reported to be nutritionally specialized relative to non-plant pathogenic pseudomonads. We performed comparative analyses of metabolic networks reconstructed from genome sequence data in order to investigate the hypothesis that P. syringae has evolved to be metabolically specialized for a plant pathogenic lifestyle. We used the metabolic network comparison tool Rahnuma and complementary bioinformatic analyses to compare the distribution of 1299 metabolic reactions across nine genome-sequenced strains of Pseudomonas, including three strains of P. syringae. The two pathogenic Pseudomonas species analyzed, P. syringae and the opportunistic human pathogen Pseudomonas aeruginosa, each displayed a high level of intra-species metabolic similarity compared to non-pathogenic Pseudomonas. The three P. syringae strains lacked a significant number of reactions predicted to be present in all other Pseudomonas strains analysed, which is consistent with the hypothesis that P. syringae is adapted for growth in a nutritionally constrained environment. Pathway predictions demonstrated that some of the differences detected in metabolic network comparisons could account for differences in amino acid assimilation ability reported in experimental analyses. Parsimony analysis and reaction neighborhood approaches were used to model the evolution of metabolic networks and amino acid assimilation pathways in pseudomonads. Both methods supported a model of Pseudomonas evolution in which the common ancestor of P. syringae had experienced a significant number of deletion events relative to other non-plant pathogenic pseudomonads. We discuss how the characteristic metabolic features of P. syringae could reflect adaptation to a pathogenic lifestyle.

post to: CiteULike

Random Tree-Puzzle leads to the Yule-Harding Distribution.

Publication Date: 2010 Aug 12 PMID: 20705907
Authors: Vinh, L. S. - Fuehrer, A. - von Haeseler, A.
Journal: Mol Biol Evol

Approaches to reconstruct phylogenies abound and are widely used in the study of molecular evolution. Partially through extensive simulations we are beginning to understand the potential pitfalls as well as the advantages of different methods. However, little work has been done on possible biases introduced by the methods if the input data are random and do not carry any phylogenetic signal. Although Tree-Puzzle (Strimmer and von Haeseler, 1996; Schmidt et al., 2002) has become common in phylogenetics, the resulting distribution of labelled, unrooted bifurcating trees when data do not carry any phylogenetic signal has not been investigated. Our note shows that the distribution converges to the well-known Yule-Harding distribution. However, the bias of the Yule-Harding distribution will be diminished by a tiny amount of phylogenetic information.

post to: CiteULike

Testing Founder Effect Speciation: Divergence Population Genetics of the Spoonbills Platalea regia and P. minor (Threskiornithidae, Aves).

Publication Date: 2010 Aug 12 PMID: 20705906
Authors: Yeung, C. K. - Tsai, P. W. - Chesser, R. T. - Lin, R. C. - Yao, C. T. - Tian, X. H. - Li, S. H.
Journal: Mol Biol Evol

Although founder effect speciation has been a popular theoretical model for the speciation of geographically isolated taxa, its empirical importance has remained difficult to evaluate due to the intractability of past demography, which in a founder effect speciation scenario would involve a speciational bottleneck in the emergent species and the complete cessation of gene flow following divergence. Using regression-weighted approximate Bayesian computation, we tested the validity of these two fundamental conditions of founder effect speciation in a pair of sister species with disjunct distributions: the royal spoonbill Platalea regia in Australasia and the black-faced spoonbill P. minor in eastern Asia. When compared to genetic polymorphism observed at 20 nuclear loci in the two species, simulations showed that the Founder Effect Speciation model had an extremely low posterior probability (1.55 X 10(-8)) of producing the extant genetic pattern. In contrast, speciation models that allowed for post-divergence gene flow were much more probable (posterior probabilities were 0.37 and 0.50 for the Bottleneck with Gene Flow and the Gene Flow models, respectively) and post-divergence gene flow persisted for a considerable period of time (over 80% of the divergence history in both models) following initial divergence (median=197000 generations, 95% CI: 50000-478000, for the Bottleneck with Gene Flow model; and 186000 generations, 95% CI: 45000-477000, for the Gene Flow model). Furthermore, the estimated population size reduction in P. regia to 7000 individuals (median, 95% CI: 487-12000, according to the Bottleneck with Gene Flow model) was unlikely to have been severe enough to be considered a bottleneck. Therefore, these results do not support founder effect speciation in P. regia but indicate instead that the divergence between P. regia and P. minor was probably driven by selection despite continuous gene flow. In this light, we discuss the potential importance of evolutionarily labile traits with significant fitness consequences, such as migratory behavior and habitat preference, in facilitating divergence of the spoonbills.

post to: CiteULike

Endosymbiotic Gene Transfer and Transcriptional Regulation of Transferred Genes in Paulinella chromatophora.

Publication Date: 2010 Aug 11 PMID: 20702568
Authors: Nowack, E. C. - Vogel, H. - Groth, M. - Grossman, A. R. - Melkonian, M. - Glockner, G.
Journal: Mol Biol Evol

Paulinella chromatophora is a cercozoan amoeba that contains 'chromatophores', which are photosynthetic inclusions of cyanobacterial origin. The recent discovery that chromatophores evolved independently of plastids, underwent major genome reduction, and transferred at least two genes to the host nucleus, has highlighted P. chromatophora as a model to infer early steps in the evolution of photosynthetic organelles. However, owing to the paucity of nuclear genome sequence data, the extent of endosymbiotic gene transfer (EGT) and host symbiont regulation are currently unknown. A combination of 454 and Illumina next generation sequencing enabled us to generate a comprehensive reference transcriptome dataset for P. chromatophora on which we mapped short Illumina cDNA reads generated from cultures from the dark and light phases of a diel cycle. Combined with extensive phylogenetic analyses of the deduced protein sequences, these data revealed that (1) about 0.3-0.8% of the nuclear genes were obtained by EGT, compared to 11-14% in the Plantae, (2) transferred genes show a distinct bias in that many encode small proteins involved in photosynthesis and photo-acclimation, (3) host cells established control over expression of transferred genes, and (4) not only EGT, but to a minor extent also horizontal gene transfer from organisms that presumably served as food sources, helped to shape the nuclear genome of P. chromatophora. The identification of a significant number of transferred genes involved in photosynthesis and photo-acclimation of thylakoid membranes as well as the observed transcriptional regulation of these genes strongly implies import of the encoded gene products into chromatophores, a feature previously thought to be restricted to canonical organelles. Thus, a possible mechanism by which P. chromatophora exerts control over the performance of its newly acquired photosynthetic organelle, may involve controlling the expression of nuclear-encoded, chromatophore-targeted regulatory components of the thylakoid membranes.

post to: CiteULike

Extreme positive selection on a new highly-expressed larval glycoprotein (LGP) gene in Galaxias fishes (Osmeriformes: Galaxiidae).

Publication Date: 2010 Aug 9 PMID: 20696791
Authors: Wallis, L. J. - Wallis, G. P.
Journal: Mol Biol Evol

We describe the intron-exon structure and DNA/protein sequences of a new larval glycoprotein gene (LGP) from nine species of galaxiid fish. The gene has distant similarity to Danio THP (Tamm-Horsefall urinary glycoprotein; uromodulin) and cichlid SPP120 (seminal plasma glycoprotein) due to conserved features of its zona pellucida (ZP) domain, including eight highly conserved cysteines and a consensus furin cleavage site (CFCS). Using a combination of 454 sequencing of cDNA, and exon-primed intron-spanning sequencing of genomic DNA, we obtained full sequences of the coding region (996 bp) and its intervening sequences (1459 bp). LGP shows an exceptionally strong signal of positive selection over the entire coding region, as evidenced by d(N)/d(S) values > 1. Across nine species of Galaxias, 87/332 (26%) of amino-acid residues are variable, compared with 9/386 (2%) for mitochondrial cytb in the same group of species. Across 36 interspecific pairwise comparisons, genetic distances are in all cases larger for coding region than for introns, by a factor of 2.4-fold on average. Reading frame, gene structure, splice sites and many ZP motifs are conserved across all species. Together with the fact that the gene is expressed in all species, these results argue clearly against the possibility of a pseudogene. We show by 454 sequencing and qPCR that the transcript is abundant (ca 0.5%) in newly-hatched larvae, and appears to be almost absent from a range of adult tissues. We postulate that the strong Darwinian evolution exhibited by this protein may reflect some type of immuno-protection at this vulnerable larval stage.

post to: CiteULike

Widespread losses of vomeronasal signal transduction in bats.

Publication Date: 2010 Aug 6 PMID: 20693241
Authors: Zhao, H. - Xu, D. - Zhang, S. - Zhang, J.
Journal: Mol Biol Evol

The vertebrate vomeronasal system (VNS) detects intraspecific pheromones and environmental odorants. We sequenced segments of the gene encoding Trpc2, an ion channel crucial for vomeronasal signal transduction, in 11 species that represent all main basal lineages of Yinpterochiroptera, one of the two suborders of the order Chiroptera (bats). Our sequences show that Trpc2 is a pseudogene in each of the 11 bats, suggesting that all yinpterochiropterans lack vomeronasal sensitivity. The Trpc2 sequences from four species of Yangochiroptera, the other suborder of bats, suggest vomeronasal insensitivity in some but not all yangochiropterans. These results, together with the available morphological data from the bat VNS, strongly suggest multiple and widespread losses of vomeronasal signal transduction and sensitivity in bats. Future scrutiny of the specific functions of the VNS in the few bats that still retain the VNS may help explain why it is dispensable in most bats.

post to: CiteULike

Lineage-specific Variation in Intensity of Natural Selection in Mammals.

Publication Date: 2010 Aug 5 PMID: 20688808
Authors: Toll-Riera, M. - Laurie, S. - Alba, M. M.
Journal: Mol Biol Evol

The molecular clock hypothesis states that protein-coding genes evolve at an approximately constant rate. However, as mentioned by Kimura and Ohta in their seminal paper from 1974, this is only expected to be true as long as the function and the tertiary structure of the molecule remain unaltered. An important implication of this statement is that significant deviations in the rate of evolution of a gene with respect to the species clock are likely to reflect functional and/or structural alterations. Here we present a method to identify such deviations, and apply it to a dataset of 2929 high quality coding sequence alignments corresponding to one to one orthologous genes from six mammalian species - human, macaque, mouse, rat, cow and dog. Deviated branches are defined as those that present significant alterations in both the rate of non-synonymous substitutions (dN) as well as selective pressure (dN/dS). Strikingly, we find that as many as 24.5% of the genes show branch-specific deviations in dN and dN/dS, though this is a relatively well conserved set of genes. Around half of these genes show branch-specific acceleration of evolutionary rates. Positive selection tests based on divergence data only identify 17.7% of the accelerated branches. Failure to identify positive selection in accelerated branches with an excess of radical amino acid replacements suggests these tests are conservative. Interestingly, genes with accelerated branches are significantly enriched in neural proteins, indicating that this type of protein might play a more important role than previously thought in species diversification, although they are generally not detected by positive selection tests. We discuss in detail several examples of genes which show lineage-specific evolutionary rate acceleration and are involved in synaptic transmission, chemosensory perception and ubiquitination.

post to: CiteULike

Molecular Evolution of Cytochrome c Oxidase Underlies High-Altitude Adaptation in the Bar-Headed Goose.

Publication Date: 2010 Aug 4 PMID: 20685719
Authors: Scott, G. R. - Schulte, P. M. - Egginton, S. - Scott, A. L. - Richards, J. G. - Milsom, W. K.
Journal: Mol Biol Evol

Bar-headed geese (Anser indicus) fly at up to 9000 m elevation during their migration over the Himalayas, sustaining high metabolic rates in the severe hypoxia at these altitudes. We investigated the evolution of cardiac energy metabolism and O(2) transport in this species to better understand the molecular and physiological mechanisms of high-altitude adaptation. Compared to low-altitude geese (pink-footed geese and barnacle geese), bar-headed geese had larger lungs and higher capillary densities in the left ventricle of the heart, both of which should improve O(2) diffusion during hypoxia. While myoglobin abundance and the activities of many metabolic enzymes (carnitine palmitoyltransferase, citrate synthase, 3-hydroxyacyl-coA dehydrogenase, lactate dehydrogenase, and pyruvate kinase) showed only minor variation between species, bar-headed geese had a striking alteration in the kinetics of cytochrome c oxidase (COX), the heteromeric enzyme that catalyzes O(2) reduction in oxidative phosphorylation. This was reflected by a lower maximum catalytic activity and a higher affinity for reduced cytochrome c. There were small differences between species in mRNA and protein expression of COX subunits 3 and 4, but these were inconsistent with the divergence in enzyme kinetics. However, the COX3 gene of bar-headed geese contained a non-synonymous substitution at a site that is otherwise conserved across vertebrates and resulted in a major functional change of amino acid class (Trp-116-->Arg). This mutation was predicted by structural modelling to alter the interaction between COX3 and COX1. Adaptations in mitochondrial enzyme kinetics and O(2) transport capacity may therefore contribute to the exceptional ability of bar-headed geese to fly high.

post to: CiteULike

Biased Gene Conversion Affects Patterns of Codon Usage and Amino Acid Usage in the Saccharomyces sensu stricto Group of Yeasts.

Publication Date: 2010 Aug 13 PMID: 20656793
Authors: Harrison, R. J. - Charlesworth, B.
Journal: Mol Biol Evol

Patterns of synonymous codon usage vary between organisms and are controlled by neutral processes (such as drift and mutation) as well as by selection. Here we show that an additional neutral process, GC-biased gene conversion (gBGC), plays a part in shaping patterns of both synonymous codon usage and amino acid composition in a manner dependent upon the local recombination rate. We obtain estimates of the strength of gBGC acting on synonymous sites in five species of yeast, which we find to be a much weaker force than selection. We use this to correct estimates of the strength of selection on codon usage bias, which are normally confounded by the action of gBGC. Our estimate of the rate of gBGC agrees well with an experimentally determined value obtained from Saccharomyces cerevisiae. We also find that, contrary to expectation, codon usage bias is highest in areas of intermediate levels of recombination for GC-ending optimal codons. Possible reasons for this are discussed.

post to: CiteULike

Evolutionary pattern of gene homogenization between primate-specific paralogs after human and macaque speciation using the 4-2-4 method.

Publication Date: 2010 Sep PMID: 20430861
Authors: Ezawa, K. - Ikeo, K. - Gojobori, T. - Saitou, N.
Journal: Mol Biol Evol

Homogenization of duplicated genes is an important factor for gene family evolution. In the previous study, we developed a method, named 4-2-4 here, to detect partial homogenization with high sensitivity and high specificity using quartets. A quartet is a set of four genes generated by a duplication event and the subsequent speciation of two closely related species. We searched the human and macaque genomes and found 430 nonredundant quartets, which correspond to primate-specific paralogs. The prevalence of homogenization in these quartets was 10.0% (43/430), which was ca. one-third of that (29.8% = 206/691) in the rodent-specific nonredundant quartets obtained through comparison of mouse and rat genomes. Part of this difference comes from the fact that primate paralogs tend to be more remotely located to each other than rodent paralogs, and the remainder may be explained by the inherent difference in the neutral evolutionary rate between the primate and rodent lineages. A statistical analysis taking account of the effects of false negatives uncovered negative correlations between sequence divergence and homogenization prevalence both in primates and rodents. Further statistical analyses controlling for false-negative rates and sequence divergences revealed two characteristics shared by the primate and rodent paralogs; 1) significant negative correlations of the homogenization prevalence with physical distances, and 2) no significant correlation between the prevalence and relative transcriptional orientations. Patterns of the homogenization in the genomic alignments of human-macaque quartets indicate that gene conversion, rather than unequal crossing-over, is the major cause of the homogenization.

post to: CiteULike

Low-complexity regions in Plasmodium falciparum: missing links in the evolution of an extreme genome.

Publication Date: 2010 Sep PMID: 20427419
Authors: Zilversmit, M. M. - Volkman, S. K. - DePristo, M. A. - Wirth, D. F. - Awadalla, P. - Hartl, D. L.
Journal: Mol Biol Evol

Over the past decade, attempts to explain the unusual size and prevalence of low-complexity regions (LCRs) in the proteins of the human malaria parasite Plasmodium falciparum have used both neutral and adaptive models. This past research has offered conflicting explanations for LCR characteristics and their role in, and influence on, the evolution of genome structure. Here we show that P. falciparum LCRs (PfLCRs) are not a single phenomenon, but rather consist of at least three distinct types of sequence, and this heterogeneity is the source of the conflict in the literature. Using molecular and population genetics, we show that these families of PfLCRs are evolving by different mechanisms. One of these families, named here the HighGC family, is of particular interest because these LCRs act as recombination hotspots, both in genes under positive selection for high levels of diversity which can be created by recombination (antigens) and those likely to be evolving neutrally or under negative selection (metabolic enzymes). We discuss how the discovery of these distinct species of PfLCRs helps to resolve previous contradictory studies on LCRs in malaria and contributes to our understanding of the evolution of the of the parasite's unusual genome.

post to: CiteULike

The evolution of thrombospondins and their ligand-binding activities.

Publication Date: 2010 Sep PMID: 20427418
Authors: Bentley, A. A. - Adams, J. C.
Journal: Mol Biol Evol

The extracellular matrix (ECM) is a complex, multiprotein network that has essential roles in tissue integrity and intercellular signaling in the metazoa. Thrombospondins (TSPs) are extracellular, calcium-binding glycoproteins that have biologically important roles in mammals in angiogenesis, vascular biology, connective tissues, immune response, and synaptogenesis. The evolution of these complex functional properties is poorly understood. We report here on the evolution of TSPs and their ligand-binding capacities, from comparative genomics of species representing the major phyla of metazoa and experimental analyses of the oligomerization properties of noncanonical TSPs of basal deuterostomes. Monomeric, dimeric, trimeric, and pentameric TSPs have arisen through separate evolutionary events involving gain, loss, or modification of a coiled-coil domain or distinct domains at the amino-terminus. The relative transience of monomeric forms under evolution implicates a biological importance for multivalency of the C-terminal region of TSPs. Most protostomes have a single TSP gene encoding a pentameric TSP. The pentameric form is also present in deuterostomes, and gene duplications at the origin of deuterostomes and gene loss and further gene duplication events in the vertebrate lineage gave rise to distinct forms and novel domain architectures. Parallel analysis of the major ligands of mammalian TSPs revealed that many binding activities are neofunctions representing either coevolutionary innovations in the deuterostome lineage or neofunctions of ancient molecules such as CD36. Contrasting widely conserved capacities include binding to heparan glycosaminoglycans, fibrillar collagen, or RGD-dependent integrins. These findings identify TSPs as fundamental components of the extracellular interaction systems of metazoa and thus impact understanding of the evolution of ECM networks. The widely conserved activities of TSPs in binding to ECM components or PS2 clade integrins will be relevant to use of TSPs in synthetic extracellular matrices or tissue engineering. In contrast, the neofunctions of vertebrate TSPs likely include interactions suitable for therapeutic targeting without general disruption of ECM.

post to: CiteULike

Adaptation and constraint at Toll-like receptors in primates.

Publication Date: 2010 Sep PMID: 20410160
Authors: Wlasiuk, G. - Nachman, M. W.
Journal: Mol Biol Evol

Frequent positive selection is a hallmark of genes involved in the adaptive immune system of vertebrates, but the incidence of positive selection for genes underlying innate immunity in vertebrates has not been well studied. The toll-like receptors (TLRs) of the innate immune system represent the first line of defense against pathogens. TLRs lie directly at the host-environment interface, and they target microbial molecules. Because of this, they might be subject to frequent positive selection due to coevolutionary dynamics with their microbial counterparts. However, they also recognize conserved molecular motifs, and this might constrain their evolution. Here, we investigate the evolution of the ten human TLRs in the framework of these competing ideas. We studied rates of protein evolution among primate species and we analyzed patterns of polymorphism in humans and chimpanzees. This provides a window into TLR evolution at both long and short timescales. We found a clear signature of positive selection in the rates of substitution across primates in most TLRs. Some of the implicated sites fall in structurally important protein domains, involve radical amino acid changes, or overlap with polymorphisms with known clinical associations in humans. However, within species, patterns of nucleotide variation were generally compatible with purifying selection, and these patterns differed between humans and chimpanzees and between viral and nonviral TLRs. Thus, adaptive evolution at TLRs does not appear to reflect a constant turnover of alleles and instead might be more episodic in nature. This pattern is consistent with more ephemeral pathogen-host associations rather than with long-term coevolution.

post to: CiteULike

The influence of anticodon-codon interactions and modified bases on codon usage bias in bacteria.

Publication Date: 2010 Sep PMID: 20403966
Authors: Ran, W. - Higgs, P. G.
Journal: Mol Biol Evol

Most transfer RNAs (tRNAs) can translate more than one synonymous codon, and most codons can be translated by more than one isoacceptor tRNA. The rates of translation of synonymous codons are dependent on the concentrations of the tRNAs and on the rates of pairing of each anticodon-codon combination. Translational selection causes a significant bias in codon frequencies in highly expressed genes in most bacteria. By comparing codon frequencies in high and low-expression genes, we determine which codons are preferred for each amino acid in a large sample of bacterial genomes. We relate this to the number of copies of each tRNA gene in each genome. In two-codon families, preferred codons have Watson-Crick pairs (GC and AU) between the third codon base and the wobble base of the anticodon rather than GU pairs. This suggests that these combinations are more rapidly recognized by the ribosome. In contrast, in four-codon families, preferred codons do not correspond to Watson-Crick rules. In some cases, a wobble-U tRNA can pair with all four codons. In these cases, A and U codons are preferred over G and C. This indicates that the nonstandard UU combination appears to be translated surprisingly well. Differences in modified bases at the wobble position of the anticodon appear to be responsible for the differences in behavior of tRNAs in two- and four-codon families. We discuss the way changes in the bases in the anticodon influence both the speed and the accuracy of translation. The number of tRNA gene copies and the strength of translational selection correlate with the growth rate of the organism, as we would expect if the primary cause of translational selection in bacteria is the requirement to optimize the speed of protein production.

post to: CiteULike

The enamelin genes in lizard, crocodile, and frog and the pseudogene in the chicken provide new insights on enamelin evolution in tetrapods.

Publication Date: 2010 Sep PMID: 20403965
Authors: Al-Hashimi, N. - Lafont, A. G. - Delgado, S. - Kawasaki, K. - Sire, J. Y.
Journal: Mol Biol Evol

Enamelin (ENAM) has been shown to be a crucial protein for enamel formation and mineralization. Previous molecular analyses have indicated a probable origin early in vertebrate evolution, which is supported by the presence of enamel/enameloid tissues in early vertebrates. In contrast to these hypotheses, ENAM was only characterized in mammals. Our aims were to 1) look for ENAM in representatives of nonmammalian tetrapods, 2) search for a pseudogene in the chicken genome, and 3) see whether the new sequences could bring new information on ENAM evolution. Using in silico approach and polymerase chain reaction, we obtained and characterized the messenger RNA sequences of ENAM in a frog, a lizard, and a crocodile; the genomic DNA sequences of ENAM in a frog and a lizard; and the putative sequence of chicken ENAM pseudogene. The comparison with mammalian ENAM sequences has revealed 1) the presence of an additional coding exon, named exon 8b, in sauropsids and marsupials, 2) a simpler 5'-untranslated region in nonmammalian ENAMs, 3) many sequence variations in the large exons while there are a few conserved regions in small exons, and 4) 25 amino acids that have been conserved during 350 million years of tetrapod evolution and hence of crucial biological importance. The chicken pseudogene was identified in a region that was not expected when considering the gene synteny in mammals. Together with the location of lizard ENAM in a homologous region, this result indicates that enamel genes were probably translocated in an ancestor of the sauropsid lineage. This study supports the origin of ENAM earlier in vertebrate evolution, confirms that tooth loss in modern birds led to the invalidation of enamel genes, and adds information on the important role played by, for example, the phosphorylated serines and the glycosylated asparagines for correct ENAM functions.

post to: CiteULike

Evolution in regulatory regions rapidly compensates the cost of nonoptimal codon usage.

Publication Date: 2010 Sep PMID: 20403964
Authors: Amoros-Moya, D. - Bedhomme, S. - Hermann, M. - Bravo, I. G.
Journal: Mol Biol Evol

The redundant genetic code contains synonymous codons, whose relative frequencies vary among species. Nonoptimal codon usage lowers gene translation efficiency, potentially leading to a fitness cost. This is particularly relevant for horizontal gene transfer, common among bacteria and a key player in antibiotic resistance propagation. By mimicking the horizontal transfer of an antibiotic resistance gene, we established that a nonoptimal codon usage renders Escherichia coli 10-20 times more sensitive to the antibiotic. After 350 generations of experimental evolution under antibiotic selection pressure, this cost was compensated through both in cis changes in the gene promoter and in trans changes in the host bacterial genome, without introducing mutations in the coding sequence of the resistance gene. Further, we have found experimental evidence for convergent molecular adaptive evolution. The high fitness cost of nonoptimal codon usage remains a minor obstacle to gene fixation upon horizontal transfer. Our results highlight the importance of rapid evolution of regulatory mechanisms in the adaptation to new environmental and genetic situations.

post to: CiteULike

The effect of mobile element IS10 on experimental regulatory evolution in Escherichia coli.

Publication Date: 2010 Sep PMID: 20400481
Authors: Stoebel, D. M. - Dorman, C. J.
Journal: Mol Biol Evol

Mobile genetic elements are widespread in bacteria, where they cause several kinds of mutations. Although their effects are on the whole negative, rare beneficial mutations caused by insertion sequence elements are frequently selected in some experimental evolution systems. For example, in earlier work, we found that strains of Escherichia coli that lack the sigma factor RpoS adapt to a high-osmolarity environment by the insertion of element IS10 into the promoter of the otsBA operon, rewiring expression from RpoS dependent to RpoS independent. We wished to determine how the presence of IS10 in the genome of this strain shaped the evolutionary outcome. IS10 could influence the outcome by causing mutations that confer adaptive phenotypes that cannot be achieved by strains without the element. Alternatively, IS10 could influence evolution by increasing the rate of appearance of certain classes of beneficial mutations even if they are no better than those that could be achieved by a strain without the element. We found that populations evolved from an IS10-free strain did not upregulate otsBA. An otsBA-lacZY fusion facilitated the recovery of a number of mutations that upregulate otsB without involving IS10 and found that two caused greater fitness increases than IS10 insertion, implying that evolution could have upregulated otsBA in the IS10-free strain. Finally, we demonstrate that there is epistasis between the IS10 insertion into the otsBA promoter and the other adaptive mutations, implying that introduction of IS10 into the otsBA promoter may alter the trajectory of adaptive evolution. We conclude that IS10 exerts its effect not by creating adaptive phenotypes that could not otherwise occur but by increasing the rate of appearance of certain adaptive mutations.

post to: CiteULike

Comprehensive analysis of simple sequence repeats in pre-miRNAs.

Publication Date: 2010 Aug 5 PMID: 20395311
Authors: Chen, M. - Tan, Z. - Zeng, G. - Peng, J.
Journal: Mol Biol Evol

Simple sequence repeats (SSRs) are tandem repeat units of 1-6 bp that are identified in various complete sequences. However, the distribution, nature and origination of SSRs in pre-miRNAs are still not well studied. The availability of large numbers of pre-miRNAs makes it possible to analyze and compare the occurrences of SSRs, the relative count of SSRs, or the longest SSRs in pre-miRNAs. In this study, we analyzed SSRs in 8619 pre-miRNAs from 87 species including Arthropoda, Nematoda, Platyhelminthes, Urochordata, Vertebrata, Mycetozoa, Protistae, Viridiplantae and Viruses. We find that SSRs widely exist in the pre-miRNAs analyzed. Our analysis shows that mononucleotide repeats are the most abundant repeats, followed by dinucleotide repeats, whereas tri-, tetra-, penta- and hexanucleotide repeats rarely occurred in pre-miRNAs. The number of SSRs per pre-miRNA on average ranges from 4.1 for viruses to 13.5 for Mycetozoa. Our results confirm that the number of repeats correlates inversely to the length of repeats. Generally, in each taxonomic group, the occurrence and relative count of SSRs decrease with the increase of repeat unit. SSRs do not exhibit obvious preference for special location in pre-miRNAs. The repeats in pre-miRNAs are complementary to repeats in coding or noncoding regions of genomes, and no significant difference is observed between these two classes with respect to the occurrence of repeats. These data on SSRs may become a useful resource of pre-miRNAs, and their possible functions are discussed.

post to: CiteULike

Parallel genetic and phenotypic evolution of DNA superhelicity in experimental populations of Escherichia coli.

Publication Date: 2010 Sep PMID: 20392810
Authors: Crozat, E. - Winkworth, C. - Gaffe, J. - Hallin, P. F. - Riley, M. A. - Lenski, R. E. - Schneider, D.
Journal: Mol Biol Evol

DNA supercoiling is the master function that interconnects chromosome structure and global gene transcription. This function has recently been shown to be under strong selection in Escherichia coli. During the evolution of 12 initially identical populations propagated in a defined environment for 20,000 generations, parallel increases in DNA supercoiling were observed in ten populations. The genetic changes associated with the increased supercoiling were examined in one population, and beneficial mutations in the genes topA (encoding topoisomerase I) and fis (encoding a histone-like protein) were identified. To elucidate the molecular basis and impact of these changes, we quantified the level of genetic, phenotypic, and molecular parallelism linked to DNA supercoiling in all 12 evolving populations. First, sequence determination of DNA topology-related loci revealed strong genetic parallelism, with mutations concentrated in three genes (topA, fis, and dusB), although the populations had different alleles at each locus. Statistical analyses of these polymorphisms implied the action of positive selection and, moreover, suggested that fis and dusB, which belong to the same operon, have related functions. Indeed, we demonstrated that DusB regulates the expression of fis by both experimental and phylogenetic analyses. Second, molecular analyses of five mutations in fis and dusB affecting the transcription, translation, and protein activity of Fis also revealed strong parallelism in the resulting phenotypic effects. Third, artificially increasing DNA supercoiling in one of the two populations that lacked DNA topology changes led to a significant fitness increase. The high levels of molecular and genetic parallelism, targeting a small subset of the many genes involved in DNA supercoiling, indicate that changes in DNA superhelicity have been important in the evolution of these populations. Surprisingly, however, most of the evolved alleles we tested had either no detectable or slightly deleterious effects on fitness, despite these signatures of positive selection.

post to: CiteULike

Compositional heterogeneity and phylogenomic inference of metazoan relationships.

Publication Date: 2010 Sep PMID: 20382658
Authors: Nesnidal, M. P. - Helmkampf, M. - Bruchhaus, I. - Hausdorf, B.
Journal: Mol Biol Evol

Compositional heterogeneity of sequences between taxa may cause systematic error in phylogenetic inference. The potential influence of such bias might be mitigated by strategies to reduce compositional heterogeneity in the data set or by phylogeny reconstruction methods that account for compositional heterogeneity. We adopted several of these strategies to analyze a large ribosomal protein data set representing all major metazoan taxa. Posterior predictive tests revealed that there is compositional bias in this data set. Only a few taxa with strongly deviating amino acid composition had to be excluded to reduce this bias. Thus, this is a good solution, if these taxa are not central to the phylogenetic question at hand. Deleting individual proteins from the data matrix may be an appropriate method, if compositional heterogeneity among taxa is concentrated in a few proteins. However, half of the ribosomal proteins had to be excluded to reduce the compositional heterogeneity to a degree that the CAT model was no longer significantly violated. Recoding of amino acids into groups is another alternative but causes a loss of information and may result in badly resolved trees as demonstrated by the present data set. Bayesian inference with the CAT-BP model directly accounts for compositional heterogeneity between lineages by introducing breakpoints along the branches of the phylogeny at which the amino acid composition is allowed to change but is computationally expensive. Finally, a neighbor joining tree based on equal input distances that consider pattern and rate heterogeneity showed several unusual groupings, which are most likely artifacts, probably caused by the loss of information resulting from the transformation of the sequence data into distances. As long as no more efficient phylogenetic inference methods are available that can directly account for compositional heterogeneity in large data sets, using methods for reducing compositional heterogeneity in the data in combination with methods that assume a stationary amino acid composition remains an option for controlling systematic errors in tree reconstruction that result from compositional bias. Our analyses indicated that the paraphyly of Deuterostomia in some analyses is the result of systematic errors that also affected the relationships of Entoprocta and Ectoprocta.

post to: CiteULike

Biosynthesis of wyosine derivatives in tRNA: an ancient and highly diverse pathway in Archaea.

Publication Date: 2010 Sep PMID: 20382657
Authors: de Crecy-Lagard, V. - Brochier-Armanet, C. - Urbonavicius, J. - Fernandez, B. - Phillips, G. - Lyons, B. - Noma, A. - Alvarez, S. - Droogmans, L. - Armengaud, J. - Grosjean, H.
Journal: Mol Biol Evol

Wyosine (imG) and its derivatives such as wybutosine (yW) are found at position 37 of phenylalanine-specific transfer RNA (tRNA(Phe)), 3' adjacent to the anticodon in Eucarya and Archaea. In Saccharomyces cerevisiae, formation of yW requires five enzymes acting in a strictly sequential order: Trm5, Tyw1, Tyw2, Tyw3, and Tyw4. Archaea contain wyosine derivatives, but their diversity is greater than in eukaryotes and the corresponding biosynthesis pathways still unknown. To identify these pathways, we analyzed the phylogenetic distribution of homologues of the yeast wybutosine biosynthesis proteins in 62 archaeal genomes and proposed a scenario for the origin and evolution of wyosine derivatives biosynthesis in Archaea that was partly experimentally validated. The key observations were 1) that four of the five wybutosine biosynthetic enzymes are ancient and may have been present in the last common ancestor of Archaea and Eucarya, 2) that the variations in the distribution pattern of biosynthesis enzymes reflect the diversity of the wyosine derivatives found in different Archaea. We also identified 7-aminocarboxypropyl-demethylwyosine (yW-86) and its N4-methyl derivative (yW-72) as final products in tRNAs of several Archaea when these were previously thought to be only intermediates of the eukaryotic pathway. We confirmed that isowyosine (imG2) and 7-methylwyosine (mimG) are two archaeal-specific guanosine-37 derivatives found in tRNA of both Euryarchaeota and Crenarchaeota. Finally, we proposed that the duplication of the trm5 gene in some Archaea led to a change in function from N1 methylation of guanosine to C7 methylation of 4-demethylwyosine (imG-14).

post to: CiteULike

Improved phylogenomic taxon sampling noticeably affects nonbilaterian relationships.

Publication Date: 2010 Sep PMID: 20378579
Authors: Pick, K. S. - Philippe, H. - Schreiber, F. - Erpenbeck, D. - Jackson, D. J. - Wrede, P. - Wiens, M. - Alie, A. - Morgenstern, B. - Manuel, M. - Worheide, G.
Journal: Mol Biol Evol

Despite expanding data sets and advances in phylogenomic methods, deep-level metazoan relationships remain highly controversial. Recent phylogenomic analyses depart from classical concepts in recovering ctenophores as the earliest branching metazoan taxon and propose a sister-group relationship between sponges and cnidarians (e.g., Dunn CW, Hejnol A, Matus DQ, et al. (18 co-authors). 2008. Broad phylogenomic sampling improves resolution of the animal tree of life. Nature 452:745-749). Here, we argue that these results are artifacts stemming from insufficient taxon sampling and long-branch attraction (LBA). By increasing taxon sampling from previously unsampled nonbilaterians and using an identical gene set to that reported by Dunn et al., we recover monophyletic Porifera as the sister group to all other Metazoa. This suggests that the basal position of the fast-evolving Ctenophora proposed by Dunn et al. was due to LBA and that broad taxon sampling is of fundamental importance to metazoan phylogenomic analyses. Additionally, saturation in the Dunn et al. character set is comparatively high, possibly contributing to the poor support for some nonbilaterian nodes.

post to: CiteULike

Combined EST and proteomic analysis identifies rapidly evolving seminal fluid proteins in Heliconius butterflies.

Publication Date: 2010 Sep PMID: 20375075
Authors: Walters, J. R. - Harrison, R. G.
Journal: Mol Biol Evol

Seminal fluid proteins (SFPs) directly influence a wide range of reproductive processes, including fertilization, sperm storage, egg production, and immune response. Like many other reproductive proteins, the molecular evolution of SFPs is generally characterized by rapid and frequently adaptive evolution. However, the evolutionary processes underlying this often-documented pattern have not yet been confidently determined. A robust understanding of the processes governing SFP evolution will ultimately require identifying SFPs and characterizing their evolution in many different taxa, often where only limited genomic resources are available. Here, we report the first comprehensive molecular genetic and evolutionary analysis of SFPs conducted in Lepidoptera (moths and butterflies). We have identified 51 novel SFPs from two species of Heliconius butterflies (Heliconius erato and Heliconius melpomene) by combining "indirect" bioinformatic and expression analyses of expressed sequence tags from male accessory gland and wing tissues with "direct" proteomic analyses of spermatophores. Proteomic analyses identified fewer SFPs than the indirect criteria but gave consistent results. Of 51 SFPs, 40 were identified in both species but fewer than half could be functionally annotated via similarity searches (Blast, IPRscan, etc.). The majority of annotated Heliconius SFPs were predicted to be chymotrypsins. Comparisons of Heliconius SFPs with those from fruit fly, mosquito, honeybee, and cricket suggest that gene turnover is high among these proteins and that SFPs are rarely conserved across insect orders. Pairwise estimates of evolutionary rates between SFPs and nonreproductive proteins show that, on average, Heliconius SFPs are evolving rapidly. At least one of these SFPs is evolving adaptively (dN/dS > 1), implicating a role for positive selection in this rapid evolution. This work establishes a strong precedent for future research on the causes and consequences of reproductive protein evolution in the Lepidoptera. Butterflies and moths have an extremely rich history of organismal research, which will provide an informative ecological context for further molecular evolutionary investigations.

post to: CiteULike

Evolution and cytological diversification of the green seaweeds (Ulvophyceae).

Publication Date: 2010 Sep PMID: 20368268
Authors: Cocquyt, E. - Verbruggen, H. - Leliaert, F. - De Clerck, O.
Journal: Mol Biol Evol

The Ulvophyceae, one of the four classes of the Chlorophyta, is of particular evolutionary interest because it features an unrivaled morphological and cytological diversity. Morphological types range from unicells and simple multicellular filaments to sheet-like and complex corticated thalli. Cytological layouts range from typical small cells containing a single nucleus and chloroplast to giant cells containing millions of nuclei and chloroplasts. In order to understand the evolution of these morphological and cytological types, the present paper aims to assess whether the Ulvophyceae are monophyletic and elucidate the ancient relationships among its orders. Our approach consists of phylogenetic analyses (maximum likelihood and Bayesian inference) of seven nuclear genes, small subunit nuclear ribosomal DNA and two plastid markers with carefully chosen partitioning strategies, and models of sequence evolution. We introduce a procedure for fast site removal (site stripping) targeted at improving phylogenetic signal in a particular epoch of interest and evaluate the specificity of fast site removal to retain signal about ancient relationships. From our phylogenetic analyses, we conclude that the ancestral ulvophyte likely was a unicellular uninucleate organism and that macroscopic growth was achieved independently in various lineages involving radically different mechanisms: either by evolving multicellularity with coupled mitosis and cytokinesis (Ulvales-Ulotrichales and Trentepohliales), by obtaining a multinucleate siphonocladous organization where every nucleus provides for its own cytoplasmic domain (Cladophorales and Blastophysa), or by developing a siphonous organization characterized by either one macronucleus or millions of small nuclei and cytoplasmic streaming (Bryopsidales and Dasycladales). We compare different evolutionary scenarios giving rise to siphonous and siphonocladous cytologies and argue that these did not necessarily evolve from a multicellular or even multinucleate state but instead could have evolved independently from a unicellular ancestor.

post to: CiteULike

Evolution of characterized phosphorylation sites in budding yeast.

Publication Date: 2010 Sep PMID: 20368267
Authors: Ba, A. N. - Moses, A. M.
Journal: Mol Biol Evol

Phosphorylation is one of the most studied and important regulatory mechanisms that modulate protein function in eukaryotic cells. Recently, several studies have investigated the evolution of phosphorylation sites identified by high-throughput methods. These studies have revealed varying degrees of evidence for constraint and plasticity, and therefore, there is currently no consensus as to the evolutionary properties of this important regulatory mechanism. Here, we present a study of high-confidence annotated sites from budding yeast and show that these sites are significantly constrained compared with their flanking region in closely related species. We show that this property does not change in structured or unstructured regions. We investigate the birth, death and compensation rates of the phosphorylation sites and test if sites are more likely to be gained or lost in proteins with greater numbers of sites. Finally, we also show that this evolutionary conservation can yield significant improvement for kinase target predictions when the kinase recognition motif is known, and can be used to infer the recognition motif when a set of targets is known. Our analysis indicates that phosphorylation sites are under selective constraint, consistent with their functional importance. We also find that a small fraction of phosphorylation sites turnover during evolution, which may be an important process underlying the evolution of regulatory networks.

post to: CiteULike

Robustness of ancestral sequence reconstruction to phylogenetic uncertainty.

Publication Date: 2010 Sep PMID: 20368266
Authors: Hanson-Smith, V. - Kolaczkowski, B. - Thornton, J. W.
Journal: Mol Biol Evol

Ancestral sequence reconstruction (ASR) is widely used to formulate and test hypotheses about the sequences, functions, and structures of ancient genes. Ancestral sequences are usually inferred from an alignment of extant sequences using a maximum likelihood (ML) phylogenetic algorithm, which calculates the most likely ancestral sequence assuming a probabilistic model of sequence evolution and a specific phylogeny--typically the tree with the ML. The true phylogeny is seldom known with certainty, however. ML methods ignore this uncertainty, whereas Bayesian methods incorporate it by integrating the likelihood of each ancestral state over a distribution of possible trees. It is not known whether Bayesian approaches to phylogenetic uncertainty improve the accuracy of inferred ancestral sequences. Here, we use simulation-based experiments under both simplified and empirically derived conditions to compare the accuracy of ASR carried out using ML and Bayesian approaches. We show that incorporating phylogenetic uncertainty by integrating over topologies very rarely changes the inferred ancestral state and does not improve the accuracy of the reconstructed ancestral sequence. Ancestral state reconstructions are robust to uncertainty about the underlying tree because the conditions that produce phylogenetic uncertainty also make the ancestral state identical across plausible trees; conversely, the conditions under which different phylogenies yield different inferred ancestral states produce little or no ambiguity about the true phylogeny. Our results suggest that ML can produce accurate ASRs, even in the face of phylogenetic uncertainty. Using Bayesian integration to incorporate this uncertainty is neither necessary nor beneficial.

post to: CiteULike

Using time-structured data to estimate evolutionary rates of double-stranded DNA viruses.

Publication Date: 2010 Sep PMID: 20363828
Authors: Firth, C. - Kitchen, A. - Shapiro, B. - Suchard, M. A. - Holmes, E. C. - Rambaut, A.
Journal: Mol Biol Evol

Double-stranded (ds) DNA viruses are often described as evolving through long-term codivergent associations with their hosts, a pattern that is expected to be associated with low rates of nucleotide substitution. However, the hypothesis of codivergence between dsDNA viruses and their hosts has rarely been rigorously tested, even though the vast majority of nucleotide substitution rate estimates for dsDNA viruses are based upon this assumption. It is therefore important to estimate the evolutionary rates of dsDNA viruses independent of the assumption of host-virus codivergence. Here, we explore the use of temporally structured sequence data within a Bayesian framework to estimate the evolutionary rates for seven human dsDNA viruses, including variola virus (VARV) (the causative agent of smallpox) and herpes simplex virus-1. Our analyses reveal that although the VARV genome is likely to evolve at a rate of approximately 1 x 10(-5) substitutions/site/year and hence approaching that of many RNA viruses, the evolutionary rates of many other dsDNA viruses remain problematic to estimate. Synthetic data sets were constructed to inform our interpretation of the substitution rates estimated for these dsDNA viruses and the analysis of these demonstrated that given a sequence data set of appropriate length and sampling depth, it is possible to use time-structured analyses to estimate the substitution rates of many dsDNA viruses independently from the assumption of host-virus codivergence. Finally, the discovery that some dsDNA viruses may evolve at rates approaching those of RNA viruses has important implications for our understanding of the long-term evolutionary history and emergence potential of this major group of viruses.

post to: CiteULike

Constrained intron structures in a microsporidian.

Publication Date: 2010 Sep PMID: 20360213
Authors: Lee, R. C. - Gill, E. E. - Roy, S. W. - Fast, N. M.
Journal: Mol Biol Evol

The 2.9-Mbp genome of the microsporidian Encephalitozoon cuniculi is severely reduced and compacted, possessing only 16 known tiny spliceosomal introns. Based on motif and expression data, intron profiles were constructed to screen the genome. Twenty additional introns were predicted and verified, doubling the previous estimate. We further predict that accurate 3' splice site (3'SS) selection is accomplished via a scanning mechanism with specificity achieved by maintaining a constrained variable length between the branch point motif and 3'SS. Only introns in ribosomal protein genes exhibit positional bias, and we hypothesize that splicing could be regulating expression of these genes. The large set of new introns in non-ribosomal protein genes suggests that current models of intron loss are unlikely sufficient to explain the distribution of introns. Together, these results extend our understanding of the role of intron loss in genome evolution and contribute to a novel model for splice site selection.

post to: CiteULike

Population-level analyses indirectly reveal cryptic sex and life history traits of Pseudoperkinsus tapetis (Ichthyosporea, Opisthokonta): a unicellular relative of the animals.

Publication Date: 2010 Sep PMID: 20360212
Authors: Marshall, W. L. - Berbee, M. L.
Journal: Mol Biol Evol

We use population genetics to detect the molecular footprint of a sexual cycle, of a haploid vegetative state, and of lack of host specificity in Pseudoperkinsus tapetis, a marine unicellular relative of the animals. Prior to this study, complete life cycles were not known for any of the unicellular lineages sharing common ancestry with multicellular animals and fungi. We established the first collection of conspecific cultures of any member from the unicellular opisthokont lineage ichthyosporea, isolating 126 cultures of P. tapetis from guts of marine invertebrates ranging from clams to sea cucumbers. We sequenced fragments of the elongation factor alpha-like (EFL) and heat-shock protein 70 (HSP70) genes for a subset of our isolates. Absence of heterozygotes from the EFL locus in 52 isolates provided evidence for haploidy. Phylogenetic incongruence and a lack of support for linkage between two loci from 34 sequenced isolates signified a history of recombination consistent with a sexual cycle. Shared haplotypes in different invertebrate species showed that P. tapetis was not host specific. Based on estimates of the frequency of sex and on observations of cultures, we propose that P. tapetis is transmitted between hosts via asexual endospores. New protists are continually being discovered, and, as this study illustrates, analysis of culturable collections from natural habitats can transform a species from a near unknown to a model system for better understanding the evolution of life histories.

post to: CiteULike