Molecular Biology and Evolution - current issue

Lack of Evolutionary Conservation at Positions Important for Thermal Stability in the Yeast ODCase Protein

Jakubowska, A., Korona, R. — 2009-06-09

Mutations destabilizing the spatial structure of proteins can persist in populations if they are fixed by drift or compensated by other mutations. The prevalence and dynamics of these processes remain largely unrecognized. A suitable target to screen for both deleterious and compensatory mutations is the URA3 gene in yeast. We identified 13 positions in which a single missense substitution causes substantially strong thermal sensitivity. We then applied mild mutagenesis resulting in roughly one base substitution per gene and found that only reversions to an original amino acid can compensate for the thermal instability. However, the 13 positions are not visibly conserved across 53 species of Ascomycota, despite that the gene product is an enzyme of stable function and high efficiency. This shows how much fitness penalties for amino acid substitutions are background dependent, underscoring the role of complex intragenic interactions in the evolution of proteins.

Can Indirect Tests Detect a Known Recombination Event in Human mtDNA?

White, D. J., Gemmell, N. J. — 2009-06-09

Whether human mitochondrial DNA (mtDNA) recombines sufficiently to influence its evolution, evolutionary analysis, and disease etiology, remains equivocal. Overall, evidence from indirect studies of population genetic data suggests that recombination is not occurring at detectable levels. This may be explained by no, or low, recombination or, alternatively, current indirect tests may be incapable of detecting recombination in human mtDNA. To investigate the latter, we have tested whether six well-established indirect tests of recombination could detect recombination in a human mtDNA data set, in which its occurrence had been empirically confirmed. Three showed statistical evidence for recombination (r² vs. distance, the Homoplasy test, Neighborhood Similarity Score), and three did not (D' vs. distance, Max Chi Squared, Pairwise Homoplasy Index). Possible reasons for detection failure are discussed. Further, evidence from earlier studies suggesting a lack of recombination in mtDNA in humans is reconsidered, taking into account the appropriateness of the tests used, based on our new findings.

Is Interlineage Recombination Responsible for Low Divergence of Mitochondrial nad3 Genes in Mytilus galloprovincialis?

Burzynski, A., Smietanka, B. — 2009-06-09

The existence of mtDNA recombination in animals has been confirmed by several case studies. Still, for Mytilus mussels possessing two divergent mitochondrial genomes (M and F), which can recombine, no recombination between coding sequences of highly diverged M and F genomes has been shown. Based on the full sequences of both genomes, it has been suggested that particularly low divergence observed within the mitochondrial nad3 gene of the Mytilus galloprovincialis mussel may be caused by its exceptionally low evolutionary rate. Here, we contribute a new pair of mitochondrial genomes typical for M. galloprovincialis and show that this low divergence is not a sign of evolutionary conservation but is rather caused by the acquisition of an F-related sequence by the published M genome of M. galloprovincialis. The most likely scenario for this apparent mtDNA-coding region recombination case is an assembly artifact.

Molecular Evolution and Functional Diversification of Fatty Acid Desaturases after Recurrent Gene Duplication in Drosophila

Fang, S., Ting, C.-T., Lee, C.-R., Chu, K.-H., Wang, C.-C., Tsaur, S.-C. — 2009-06-09

Frequent gene duplications in the genome incessantly supply new genetic materials for functional innovation presumably driven by positive Darwinian selection. This mechanism in the desaturase gene family has been proposed to be important in triggering the pheromonal diversification in insects. With the recent completion of a dozen Drosophila genomes, a genome-wide perspective is possible. In this study, we first identified homologs of desaturase genes in 12 Drosophila species and noted that while gene duplication events are relatively frequent, gene losses are not scarce, especially in the desat1–desat2–desatF clade. By reconciling the gene tree with species phylogeny and the chromosomal synteny of the sequenced Drosophila genomes, at least one gene loss in desat2 and a minimum of six gene gains (resulting in seven desatF homologs, -), three gene losses and one relocation in desatF were inferred. Upon branching off the ancestral desat1 lineage, both desat2 and desatF gained novel functions through accelerating protein evolution. The amino acid residues under positive selection located near the catalytic sites and the C-terminal region might be responsible for altered substrate selectivity between closely related species. The association between the expression pattern of desatF- and the chemical composition of cuticular hydrocarbons implies that the ancestral function of desatF- is the second desaturation at the four carbons after the first double bond in diene synthesis, and the shift from bisexual to female-specific expression in desatF- occurred in the ancestral lineage of Drosophila melanogaster subgroup. A relationship between the number of expressed desatF homologs and the diene diversification has also been observed. These results suggest that the molecular diversification of fatty acid desaturases after recurrent gene duplication plays an important role in pheromonal diversity in Drosophila.

A Permutation Test of Host-Parasite Cospeciation

Hommola, K., Smith, J. E., Qiu, Y., Gilks, W. R. — 2009-06-09

We introduce a statistical method that explores host–parasite coevolution by testing the null hypothesis that hosts and their associated parasites evolved independently. This test is simple and intuitive and involves only suitable randomization of the observed data. It is not even necessary to construct host and parasite phylogenetic trees, as the test can be performed directly on distance matrices. Statistical power of the test was evaluated using simulated data consistent with the alternative hypothesis of cospeciation. Results were compared with the method of Mantel (1967) and the ParaFit method of Legendre et al. (2002). We observed that our method has greater power overall and thus a higher ability to detect cospeciation in closely related host–parasite systems. Our test was also successful when applied to the pocket gopher and chewing lice system.

Origin and Ascendancy of a Chimeric Fusion Gene: The {beta}/{delta}-Globin Gene of Paenungulate Mammals

Opazo, J. C., Sloan, A. M., Campbell, K. L., Storz, J. F. — 2009-06-09

The -globin gene (HBD) of eutherian mammals exhibits a propensity for recombinational exchange with the closely linked β-globin gene (HBB) and has been independently converted by the HBB gene in multiple lineages. Here we report the presence of a chimeric β/ fusion gene in the African elephant (Loxodonta africana) that was created by unequal crossing-over between misaligned HBD and HBB paralogs. The recombinant chromosome that harbors the β/ fusion gene in elephants is structurally similar to the "anti-Lepore" duplication mutant of humans (the reciprocal exchange product of the hemoglobin Lepore deletion mutant). However, the situation in the African elephant is unique in that the chimeric β/ fusion gene supplanted the parental HBB gene and is therefore solely responsible for synthesizing the β-chain subunits of adult hemoglobin. A phylogenetic survey of β-like globin genes in afrotherian and xenarthran mammals revealed that the origin of the chimeric β/ fusion gene and the concomitant inactivation of the HBB gene predated the radiation of "Paenungulata," a clade of afrotherian mammals that includes three orders: Proboscidea (elephants), Sirenia (dugongs and manatees), and Hyracoidea (hyraxes). The reduced fitness of the human Hb Lepore deletion mutant helps to explain why independently derived β/ fusion genes (which occur on an anti-Lepore chromosome) have been fixed in a number of mammalian lineages, whereas the reciprocal /β fusion gene (which occurs on a Lepore chromosome) has yet to be documented in any nonhuman mammal. This illustrates how the evolutionary fates of chimeric fusion genes can be strongly influenced by their recombinational mode of origin.

Inferring Population Mutation Rate and Sequencing Error Rate Using the SNP Frequency Spectrum in a Sample of DNA Sequences

Liu, X., Maxwell, T. J., Boerwinkle, E., Fu, Y.-X. — 2009-06-09

One challenge of analyzing samples of DNA sequences is to account for the nonnegligible polymorphisms produced by error when the sequencing error rate is high or the sample size is large. Specifically, those artificial sequence variations will bias the observed single nucleotide polymorphism (SNP) frequency spectrum, which in turn may further bias the estimators of the population mutation rate $$\theta =4N\mu $$ for diploids. In this paper, we propose a new approach based on the generalized least squares (GLS) method to estimate , given a SNP frequency spectrum in a random sample of DNA sequences from a population. With this approach, error rate can be either known or unknown. In the latter case, can be estimated given an estimation of . Using coalescent simulation, we compared our estimators with other estimators of . The results showed that the GLS estimators are more efficient than other estimators with error, and the estimation of is usable in practice when the per bp is small. We demonstrate the application of the estimators with 10-kb noncoding region sequence sampled from a human population and provide suggestions for choosing estimators with error.

Evolution of the Vertebrate Gene Regulatory Network Controlled by the Transcriptional Repressor REST

Johnson, R., Samuel, J., Ng, C. K. L., Jauch, R., Stanton, L. W., Wood, I. C. — 2009-06-09

Specific wiring of gene-regulatory networks is likely to underlie much of the phenotypic difference between species, but the extent of lineage-specific regulatory architecture remains poorly understood. The essential vertebrate transcriptional repressor REST (RE1-Silencing Transcription Factor) targets many neural genes during development of the preimplantation embryo and the central nervous system, through its cognate DNA motif, the RE1 (Repressor Element 1). Here we present a comparative genomic analysis of REST recruitment in multiple species by integrating both sequence and experimental data. We use an accurate, experimentally validated Position-Specific Scoring Matrix method to identify REST binding sites in multiply aligned vertebrate genomes, allowing us to infer the evolutionary origin of each of 1,298 human RE1 elements. We validate these findings using experimental data of REST binding across the whole genomes of human and mouse. We show that one-third of human RE1s are unique to primates: These sites recruit REST in vivo, target neural genes, and are under purifying evolutionary selection. We observe a consistent and significant trend for more ancient RE1s to have higher affinity for REST than lineage-specific sites and to be more proximal to target genes. Our results lead us to propose a model where new transcription factor binding sites are constantly generated throughout the genome; thereafter, refinement of their sequence and location consolidates this remodeling of networks governing neural gene regulation.

Calcium-Activated Potassium (BK) Channels Are Encoded by Duplicate slo1 Genes in Teleost Fishes

Rohmann, K. N., Deitcher, D. L., Bass, A. H. — 2009-06-09

Calcium-activated, large conductance potassium (BK) channels in tetrapods are encoded by a single slo1 gene, which undergoes extensive alternative splicing. Alternative splicing generates a high level of functional diversity in BK channels that contributes to the wide range of frequencies electrically tuned by the inner ear hair cells of many tetrapods. To date, the role of BK channels in hearing among teleost fishes has not been investigated at the molecular level, although teleosts account for approximately half of all extant vertebrate species. We identified slo1 genes in teleost and nonteleost fishes using polymerase chain reaction and genetic sequence databases. In contrast to tetrapods, all teleosts examined were found to express duplicate slo1 genes in the central nervous system, whereas nonteleosts that diverged prior to the teleost whole-genome duplication event express a single slo1 gene. Phylogenetic analyses further revealed that whereas other slo1 duplicates were the result of a single duplication event, an independent duplication occurred in a basal teleost (Anguilla rostrata) following the slo1 duplication in teleosts. A third, independent slo1 duplication (autotetraploidization) occurred in salmonids. Comparison of teleost slo1 genomic sequences to their tetrapod orthologue revealed a reduced number of alternative splice sites in both slo1 co-orthologues. For the teleost Porichthys notatus, a focal study species that vocalizes with maximal spectral energy in the range electrically tuned by BK channels in the inner ear, peripheral tissues show the expression of either one (e.g., vocal muscle) or both (e.g., inner ear) slo1 paralogues with important implications for both auditory and vocal physiology. Additional loss of expression of one slo1 paralogue in nonneural tissues in P. notatus suggests that slo1 duplicates were retained via subfunctionalization. Together, the results predict that teleost fish achieve a diversity of BK channel subfunction via gene duplication, rather than increased alternative splicing as witnessed for the tetrapod and invertebrate orthologue.

Variation in the Ratio of Nucleotide Substitution and Indel Rates across Genomes in Mammals and Bacteria

Chen, J.-Q., Wu, Y., Yang, H., Bergelson, J., Kreitman, M., Tian, D. — 2009-06-09

Rates of nucleotide substitution and insertion/deletion (indel) are known to vary across the functional components of a genome. Little attention has been paid, however, to the quantitative relationship between the two. Here we investigate the ratio of nucleotide substitutions to indels (S/I) in different regions of 4 primates, 70 bacteria, and 8 other genomes. We find that the ratio differs at 5.4-times between coding and noncoding, 3.3-times between conserved and less conserved coding sequences, and 1.46-times between nonrepeat and repeat regions. The S/I ratio is also positively correlated with the level of divergence between the genomes compared. Our results suggest that the S/I ratio may reflect differences in the efficacy of selection against indels. Due to the sensitivity of indel density in different regions, this ratio varies over a much larger range. With the recent discovery suggesting that indels act as local enhancers of mutation in surrounding sequences, nucleotide substitution rates are expected to be accelerated in regions of low constraint, where indels tend to accumulate, but will otherwise be modulated in proportion to the level of a sequence's functional constraint. Indels, therefore, may play a nontrivial role in controlling differences in genetic variation and divergence across functional regions of a genome.

A Proteomic Survey of Chlamydomonas reinhardtii Mitochondria Sheds New Light on the Metabolic Plasticity of the Organelle and on the Nature of the {alpha}-Proteobacterial Mitochondrial Ancestor

2009-06-09

Mitochondria play a key role in the life and death of eukaryotic cells, yet the full spectrum of mitochondrial functions is far from being fully understood, especially in photosynthetic organisms. To advance our understanding of mitochondrial functions in a photosynthetic cell, an extensive proteomic survey of Percoll-purified mitochondria from the metabolically versatile, hydrogen-producing green alga Chlamydomonas reinhardtii was performed. Different fractions of purified mitochondria from Chlamydomonas cells grown under aerobic conditions were analyzed by nano-liquid chromatography–electrospray ionization–mass spectrometry after protein separation on sodium dodecyl sulfate polyacrylamide gel electrophoresis or on blue-native polyacrylamide gel electrophoresis. Of the 496 nonredundant proteins identified, 149 are known or predicted to reside in other cellular compartments and were thus excluded from the molecular and evolutionary analyses of the Chlamydomonas proteome. The mitochondrial proteome of the photosynthetic alga reveals important lineage-specific differences with other mitochondrial proteomes, reflecting the high metabolic diversity of the organelle. Some mitochondrial metabolic pathways in Chlamydomonas appear to combine typical mitochondrial enzymes and bacterial-type ones, whereas others are unknown among mitochondriate eukaryotes. The comparison of the Chlamydomonas proteins to their identifiable homologs predicted from 354 sequenced genomes indicated that Arabidopsis is the most closely related nonalgal eukaryote. Furthermore, this phylogenomic analysis shows that free-living -proteobacteria from the metabolically versatile orders Rhizobiales and Rhodobacterales better reflect the gene content of the ancestor of the chlorophyte mitochondria than parasitic -proteobacteria with reduced and specialized genomes.

Recent Strong Positive Selection on Drosophila melanogaster HDAC6, a Gene Encoding a Stress Surveillance Factor, as Revealed by Population Genomic Analysis

Svetec, N., Pavlidis, P., Stephan, W. — 2009-06-09

Based on nearly complete genome sequences from a variety of organisms, data on naturally occurring genetic variation on the scale of hundreds of loci to entire genomes have been collected in recent years. In parallel, new statistical approaches (such as the composite likelihood ratio and "SweepFinder" tests) have been developed to infer evidence of recent positive selection from these data and to localize the target of selection. Here, we apply these methods to the X chromosome of Drosophila melanogaster in an effort to map genes involved in ecological adaptation. Using slight modifications of these tests that increase their robustness against past demographic changes, we detected evidence that recent strongly positive selection has been acting on a 2.7-kb region in an ancestral African population. This region overlaps with the 3' end of HDAC6, a gene that encodes a newly characterized stress surveillance factor. HDAC6 is an unusual histone deacetylase being localized in the cytoplasm. Its ubiquitin-binding and tubulin-deacetylase activities suggest that HDAC6 is very different from other histone deacetylases. Indeed, recent discoveries have shown that HDAC6 is a key regulator of cytotoxic stress resistance.

The Fruitless Gene in Nasonia Displays Complex Sex-Specific Splicing and Contains New Zinc Finger Domains

Bertossa, R. C., van de Zande, L., Beukeboom, L. W. — 2009-06-09

The transcription factor Fruitless exerts a broad range of functions during Drosophila development, the most apparent of which is the determination of sexual behavior in males. Although fruitless sequences are found in other insect orders, little is known about fruitless structure and function outside Diptera. We have performed a thorough analysis of fruitless transcripts in the haplo-diploid wasp Nasonia vitripennis and found both sex-specific and non–sex-specific transcripts similar to those found in Drosophila. In Nasonia, however, a novel, large fruitless transcript is present in females only. Putative binding sites for sex-specific splicing factors found in Nasonia fruitless and doublesex as well as Apis mellifera doublesex transcripts were sufficient to identify a corresponding female-specific fruitless exon in A. mellifera, suggesting that similar factors in both hymenopteran species could be responsible for sex-specific splicing of both genes. Furthermore, new C₂H₂ zinc finger domains found in Nasonia fruitless transcripts were also identified in the fruitless locus of major holometabolous insect species but not in drosophilids. Conservation of important domains and sex-specific splicing in Diptera and Hymenoptera support the hypothesis that fruitless is an ancient gene and has conserved functions in insects. Considerable divergences in other parts of the gene are expected to underlie species-specific differences and may help to explain diversity observed in insect sexual behaviors.

Translationally Optimal Codons Associate with Structurally Sensitive Sites in Proteins

Zhou, T., Weems, M., Wilke, C. O. — 2009-06-09

The mistranslation-induced protein misfolding hypothesis predicts that selection should prefer high-fidelity codons at sites at which translation errors are structurally disruptive and lead to protein misfolding and aggregation. To test this hypothesis, we analyzed the relationship between codon usage bias and protein structure in the genomes of four model organisms, Escherichia coli, yeast, fly, and mouse. Using both the Mantel–Haenszel procedure, which applies to categorical data, and a newly developed association test for continuous variables, we find that translationally optimal codons associate with buried residues and also with residues at sites where mutations lead to large changes in free energy (G). In each species, only a subset of all amino acids show this signal, but most amino acids show the signal in at least one species. By repeating the analysis on a reduced data set that excludes interdomain linkers, we show that our results are not caused by an association of rare codons with solvent-accessible linker regions. Finally, we find that our results depend weakly on expression level; the association between optimal codons and buried sites exists at all expression levels, but increases in strength as expression level increases.

Genetic and Demographic Implications of the Bantu Expansion: Insights from Human Paternal Lineages

2009-06-09

The expansion of Bantu languages, which started around 5,000 years before present in west/central Africa and spread all throughout sub-Saharan Africa, may represent one of the major and most rapid demographic movements in the history of the human species. Although the genetic footprints of this expansion have been unmasked through the analyses of the maternally inherited mitochondrial DNA lineages, information on the genetic impact of this massive movement and on the genetic composition of pre-Bantu populations is still scarce.

Here, we analyze an extensive collection of Y-chromosome markers—41 single nucleotide polymorphisms and 18 short tandem repeats—in 883 individuals from 22 Bantu-speaking agriculturalist populations and 3 Pygmy hunter-gatherer populations from Gabon and Cameroon. Our data reveal a recent origin for most paternal lineages in west Central African populations most likely resulting from the expansion of Bantu-speaking farmers that erased the more ancient Y-chromosome diversity found in this area. However, some traces of ancient paternal lineages are observed in these populations, mainly among hunter-gatherers. These results are at odds with those obtained from mtDNA analyses, where high frequencies of ancient maternal lineages are observed, and substantial maternal gene flow from hunter-gatherers to Bantu farmers has been suggested. These differences are most likely explained by sociocultural factors such as patrilocality. We also find the intriguing presence of paternal lineages belonging to Eurasian haplogroup R1b1*, which might represent footprints of demographic expansions in central Africa not directly related to the Bantu expansion.

Strong Evidence for Lineage and Sequence Specificity of Substitution Rates and Patterns in Drosophila

Singh, N. D., Arndt, P. F., Clark, A. G., Aquadro, C. F. — 2009-06-09

Rates of single nucleotide substitution in Drosophila are highly variable within the genome, and several examples illustrate that evolutionary rates differ among Drosophila species as well. Here, we use a maximum likelihood method to quantify lineage-specific substitutional patterns and apply this method to 4-fold degenerate synonymous sites and introns from more than 8,000 genes aligned in the Drosophila melanogaster group. We find that within species, different classes of sequence evolve at different rates, with long introns evolving most slowly and short introns evolving most rapidly. Relative rates of individual single nucleotide substitutions vary ~3-fold among lineages, yielding patterns of substitution that are comparatively less GC-biased in the melanogaster species complex relative to Drosophila yakuba and Drosophila erecta. These results are consistent with a model coupling a mutational shift toward reduced GC content, or a shift in mutation–selection balance, in the D. melanogaster species complex, with variation in selective constraint among different classes of DNA sequence. Finally, base composition of coding and intronic sequences is not at equilibrium with respect to substitutional patterns, which primarily reflects the slow rate of the substitutional process. These results thus support the view that mutational and/or selective processes are labile on an evolutionary timescale and that if the process is indeed selection driven, then the distribution of selective constraint is variable across the genome.

Characterization of 67 Mitochondrial tRNA Gene Rearrangements in the Hymenoptera Suggests That Mitochondrial tRNA Gene Position Is Selectively Neutral

Dowton, M., Cameron, S. L., Dowavic, J. I., Austin, A. D., Whiting, M. F. — 2009-06-09

We present entire sequences of two hymenopteran mitochondrial genomes and the major portion of three others. We combined these data with nine previously sequenced hymenopteran mitochondrial genomes. This allowed us to infer and analyze the evolution of the 67 mitochondrial gene rearrangements so far found in this order. All of these involve tRNA genes, whereas four also involve larger (protein-coding or ribosomal RNA) genes. We find that the vast majority of mitochondrial gene rearrangements are independently derived. A maximum of four of these rearrangements represent shared, derived organizations, whereas three are convergently derived. The remaining mitochondrial gene rearrangements represent new mitochondrial genome organizations. These data are consistent with the proposal that there are an enormous number of alternative mitochondrial genome organizations possible and that mitochondrial genome organization is, for the most part, selectively neutral. Nevertheless, some mitochondrial genes appear less mobile than others. Genes close to the noncoding region are generally more mobile but only marginally so. Some mitochondrial genes rearrange in a pattern consistent with the duplication/random loss model, but more mitochondrial genes move in a pattern inconsistent with this model. An increased rate of mitochondrial gene rearrangement is not tightly associated with the evolution of parasitism. Although parasitic lineages tend to have more mitochondrial gene rearrangements than nonparasitic lineages, there are exceptions (e.g., Orussus and Schlettererius). It is likely that only a small proportion of the total number of mitochondrial gene rearrangements that have occurred during the evolution of the Hymenoptera have been sampled in the present study.

The Evolutionarily Dynamic IFN-Inducible GTPase Proteins Play Conserved Immune Functions in Vertebrates and Cephalochordates

Li, G., Zhang, J., Sun, Y., Wang, H., Wang, Y. — 2009-06-09

Interferon (IFN)-inducible GTPases currently include four families of proteins: myxovirus resistant proteins (Mxs), guanylate-binding proteins (GBPs), immunity-related GTPase proteins (IRGs), and very large inducible GTPase proteins (VLIGs). They are all under conserved regulation by IFNs in humans and mice and play a critical role in preventing microbial infections. However, differences between vertebrates are poorly characterized, and their evolutionary origins have not been studied in detail. In this study, we performed comparative genomic analysis of the four families in 18 representative animals that yielded several unexpected results. Firstly, we found that Mx, GBP, and IRG protein families arose before the divergence of chordate subphyla, but VLIG emerged solely in vertebrates. Secondly, IRG, GBP, and VLIG families have experienced a high rate of gene gain and loss during the evolution, with the GBP family being lost entirely in two pufferfish and VLIG family lost in primates and carnivores. Thirdly, the regulation of these genes by IFNs is highly conserved throughout vertebrates although the VLIG protein sequences in fish have lost the first 870 amino acid residues. Finally, amphioxus IFN-inducible GTPase genes are all highly expressed in immune-related organs such as gill, liver, and intestine and are upregulated after challenge with PolyI:C and pathogens, although no IFNs or their receptors were detected in the current amphioxus genome database. These results suggest that IFN-inducible GTPase genes play conserved immune functions both in vertebrates and in cephalochordates.

Evolutionary Scenarios of Notch Proteins

Theodosiou, A., Arhondakis, S., Baumann, M., Kossida, S. — 2009-06-09

Notch is a highly conserved family of transmembrane receptors and transcription factors that are key players in several developmental processes. In this study, we identified novel Notch sequences from various species covering from worm to human and conducted a comprehensive phylogenetic analysis in order to confirm and extend the evolutionary history of Notch. Our findings confirm an independent duplication event in Caenorhabditis elegans resulting in two Notch genes and show that the vertebrate Notch genes resulted from two duplication events, both of which occurred before the divergence of teleosts and tetrapoda. Furthermore, we demonstrate that the vertebrate Notch2 group is phylogenetically closer to Notch3 and that Notch2 appeared at the first round of vertebrate duplication events. Moreover, there is evidence that the two Notch1 genes in fish, appeared by a recent duplication of Notch1 in teleost after the divergence of teleost and tetrapoda. Whether this is from ancient whole genome duplication (WGD) or gene duplication remains to be elucidated. The fourth group of Notch (Notch4) was found only in mammals. We suggest two possible scenarios for the origin of the Notch4 subfamily: 1) Notch4 appeared at the time of the two WGDs in the early chordate but has been maintained only in the mammalian lineage and was lost in the other lineages, 2) a recent independent duplication event took place in the mammalian lineage. The increase of the sequencing data from Xenopus tropicalis, Gallus gallus genome projects and of other avian and reptile genomes will shed more light on this event. Nevertheless, the great divergence of Notch4, from the other three Notch genes, suggests a rapid divergence raising questions about the functional implication of this event. In addition, comparison of the organization of Notch syntenic genes among species supports the coordinated rearrangements during evolution for Notch, PBX, and BRD families that may lead to possible functional relationships.

FastTree: Computing Large Minimum Evolution Trees with Profiles instead of a Distance Matrix

Price, M. N., Dehal, P. S., Arkin, A. P. — 2009-06-09

Gene families are growing rapidly, but standard methods for inferring phylogenies do not scale to alignments with over 10,000 sequences. We present FastTree, a method for constructing large phylogenies and for estimating their reliability. Instead of storing a distance matrix, FastTree stores sequence profiles of internal nodes in the tree. FastTree uses these profiles to implement Neighbor-Joining and uses heuristics to quickly identify candidate joins. FastTree then uses nearest neighbor interchanges to reduce the length of the tree. For an alignment with N sequences, L sites, and a different characters, a distance matrix requires O(N²) space and O(N²L) time, but FastTree requires just O(NLa + N ) memory and O(N log (N)La) time. To estimate the tree's reliability, FastTree uses local bootstrapping, which gives another 100-fold speedup over a distance matrix. For example, FastTree computed a tree and support values for 158,022 distinct 16S ribosomal RNAs in 17 h and 2.4 GB of memory. Just computing pairwise Jukes–Cantor distances and storing them, without inferring a tree or bootstrapping, would require 17 h and 50 GB of memory. In simulations, FastTree was slightly more accurate than Neighbor-Joining, BIONJ, or FastME; on genuine alignments, FastTree's topologies had higher likelihoods. FastTree is available at http://microbesonline.org/fasttree.

Sixty Million Years in Evolution of Soft Grain Trait in Grasses: Emergence of the Softness Locus in the Common Ancestor of Pooideae and Ehrhartoideae, after their Divergence from Panicoideae

Charles, M., Tang, H., Belcram, H., Paterson, A., Gornicki, P., Chalhoub, B. — 2009-06-09

Together maize, Sorghum, rice, and wheat grass (Poaceae) species are the most important cereal crops in the world and exhibit different "grain endosperm texture." This trait has been studied extensively in wheat because of its pivotal role in determining quality of products obtained from wheat grain. Grain softness protein-1 and Puroindolines A and B (grain storage proteins), encoded by Ha-like genes: Gsp-1, Pina, and Pinb, of the Hardness (Ha) locus, are the main determinants of the grain softness/hardness trait in wheat. The origin and evolution of grain endosperm texture in grasses was addressed by comparing genomic sequences of the Ha orthologous region of wheat, Brachypodium, rice, and Sorghum. Results show that the Ha-like genes are present in wheat and Brachypodium but are absent from Sorghum bicolor. A truncated remnant of an Ha-like gene is present in rice. Synteny analysis of the genomes of these grass species shows that only one of the paralogous Ha regions, created 70 My by whole-genome duplication, contained Ha-like genes. The comparative genome analysis and evolutionary comparison with genes encoding grain reserve proteins of grasses suggest that an ancestral Ha-like gene emerged, as a new member of the prolamin gene family, in a common ancestor of the Pooideae (Triticeae and Brachypoidieae tribes) and Ehrhartoideae (rice), between 60 and 50 My, after their divergence from Panicoideae (Sorghum). It was subsequently lost in Ehrhartoideae. Recurring duplications, deletions, and/or truncations occurred independently and appear to characterize Ha-like gene evolution in the grass species. The Ha-like genes gained a new function in Triticeae, such as wheat, underlying the soft grain phenotype. Loss of these genes in some wheat species leads, in turn, to hard endosperm seeds.

Computational Methods for Evaluating Phylogenetic Models of Coding Sequence Evolution with Dependence between Codons

Rodrigue, N., Kleinman, C. L., Philippe, H., Lartillot, N. — 2009-06-09

In recent years, molecular evolutionary models formulated as site-interdependent Markovian codon substitution processes have been proposed as means of mechanistically accounting for selective features over long-range evolutionary scales. Under such models, site interdependencies are reflected in the use of a simplified protein tertiary structure representation and predefined statistical potential, which, along with mutational parameters, mediate nonsynonymous rates of substitution; rates of synonymous events are solely mediated by mutational parameters. Although theoretically attractive, the models are computationally challenging, and the methods used to manipulate them still do not allow for quantitative model evaluations in a multiple-sequence context. Here, we describe Markov chain Monte Carlo computational methodologies for sampling parameters from their posterior distribution under site-interdependent codon substitution models within a phylogenetic context and allowing for Bayesian model assessment and ranking. Specifically, the techniques we expound here can form the basis of posterior predictive checking under these models and can be embedded within thermodynamic integration algorithms for computing Bayes factors. We illustrate the methods using two data sets and find that although current forms of site-interdependent models of codon substitution provide an improved fit, they are outperformed by the extended site-independent versions. Altogether, the methodologies described here should enable a quantified contrasting of alternative ways of modeling structural constraints, or other site-interdependent criteria, and establish if such formulations can match (or supplant) site-independent model extensions.

Evolution of the vertebrate twist family and synfunctionalization: a mechanism for differential gene loss through merging of expression domains

2009-06-09

Comparative Analysis of Structural Diversity and Sequence Evolution in Plant Mitochondrial Genes Transferred to the Nucleus

Liu, S.-L., Zhuang, Y., Zhang, P., Adams, K. L. — 2009-06-09