Dataset Information

Evolutionary rate analyses of orthologs and paralogs from 12 Drosophila genomes.

ABSTRACT: The newly sequenced genome sequences of 11 Drosophila species provide the first opportunity to investigate variations in evolutionary rates across a clade of closely related species. Protein-coding genes were predicted using established Drosophila melanogaster genes as templates, with recovery rates ranging from 81%-97% depending on species divergence and on genome assembly quality. Orthology and paralogy assignments were shown to be self-consistent among the different Drosophila species and to be consistent with regions of conserved gene order (synteny blocks). Next, we investigated the rates of diversification among these species' gene repertoires with respect to amino acid substitutions and to gene duplications. Constraints on amino acid sequences appear to have been most pronounced on D. ananassae and least pronounced on D. simulans and D. erecta terminal lineages. Codons predicted to have been subject to positive selection were found to be significantly over-represented among genes with roles in immune response and RNA metabolism, with the latter category including each subunit of the Dicer-2/r2d2 heterodimer. The vast majority of gene duplications (96.5%) and synteny rearrangements were found to occur, as expected, within single Müller elements. We show that the rate of ancient gene duplications was relatively uniform. However, gene duplications in terminal lineages are strongly skewed toward very recent events, consistent with either a rapid-birth and rapid-death model or the presence of large proportions of copy number variable genes in these Drosophila populations. Duplications were significantly more frequent among trypsin-like proteases and DM8 putative lipid-binding domain proteins.

SUBMITTER: Heger A

PROVIDER: S-EPMC2099592 | biostudies-literature | 2007 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Evolutionary rate analyses of orthologs and paralogs from 12 Drosophila genomes.

Heger Andreas A Ponting Chris P CP

Genome research 20071107 12

The newly sequenced genome sequences of 11 Drosophila species provide the first opportunity to investigate variations in evolutionary rates across a clade of closely related species. Protein-coding genes were predicted using established Drosophila melanogaster genes as templates, with recovery rates ranging from 81%-97% depending on species divergence and on genome assembly quality. Orthology and paralogy assignments were shown to be self-consistent among the different Drosophila species and to ...[more]

PMID: 17989258

Similar Datasets

Project description:BackgroundHarnessing vast amounts of genomic data in phylogenetic context stemming from massive sequencing of multiple closely related genomes requires new tools and approaches. We present a tool for the genome-wide analysis of frequencies and patterns of amino acid substitutions in multiple alignments of genes' coding regions, and a database of amino acid substitutions in the phylogeny of 12 Drosophila genomes. We illustrate the use of these resources to address three types of evolutionary genomics questions: about fluxes in amino acid composition in proteins, about asymmetries in amino acid substitutions and about patterns of molecular evolution in duplicated genes.ResultsWe demonstrate that amino acid composition of Drosophila proteins underwent a significant shift over the last 70 million years encompassed by the studied phylogeny, with less common amino acids (Cys, Met, His) increasing in frequency and more common ones (Ala, Leu, Glu) becoming less frequent. These fluxes are strongly correlated with polarity of source and destination amino acids, resulting in overall systematic decrease of mean polarity of amino acids found in Drosophila proteins. Frequency and radicality of amino acid substitutions are higher in paralogs than in orthologous single-copy genes and are higher in gene families with paralogs than in gene families without surviving duplications. Rate and radicality of substitutions, as expected, are negatively correlated with overall level and uniformity of gene expression. However, these correlations are not observed for substitutions occurring in duplicated genes, indicating a different selective constraint on the evolution of paralogous sequences. Clades resulting from duplications show a marked asymmetry in rate and radicality of amino acid substitutions, possibly a signal of widespread neofunctionalization. These patterns differ among protein families of different functionality, with genes coding for RNA-binding proteins differing from most other functional groups in terms of amino acid substitution patterns in duplicated and single-copy genes.ConclusionsWe demonstrate that deep phylogenetic analysis of amino acid substitutions can reveal interesting genome-wide patterns. Amino acid composition of drosophilid proteins is shaped by fluxes similar to those previously observed in prokaryotic, yeast and mammalian genomes, indicating globally present patterns. Increased frequency and radicality of amino acid substitutions in duplicated genes and the presence of asymmetry of these parameters between paralogous clades indicate widespread neofunctionalization among paralogs as the mechanism of duplication retention.

Project description:Model organisms have contributed substantially to our understanding of the etiology of human disease as well as having assisted with the development of new treatment modalities. The availability of the human, mouse and, most recently, the rat genome sequences now permit the comprehensive investigation of the rodent orthologs of genes associated with human disease. Here, we investigate whether human disease genes differ significantly from their rodent orthologs with respect to their overall levels of conservation and their rates of evolutionary change.Human disease genes are unevenly distributed among human chromosomes and are highly represented (99.5%) among human-rodent ortholog sets. Differences are revealed in evolutionary conservation and selection between different categories of human disease genes. Although selection appears not to have greatly discriminated between disease and non-disease genes, synonymous substitution rates are significantly higher for disease genes. In neurological and malformation syndrome disease systems, associated genes have evolved slowly whereas genes of the immune, hematological and pulmonary disease systems have changed more rapidly. Amino-acid substitutions associated with human inherited disease occur at sites that are more highly conserved than the average; nevertheless, 15 substituting amino acids associated with human disease were identified as wild-type amino acids in the rat. Rodent orthologs of human trinucleotide repeat-expansion disease genes were found to contain substantially fewer of such repeats. Six human genes that share the same characteristics as triplet repeat-expansion disease-associated genes were identified; although four of these genes are expressed in the brain, none is currently known to be associated with disease.Most human disease genes have been retained in rodent genomes. Synonymous nucleotide substitutions occur at a higher rate in disease genes, a finding that may reflect increased mutation rates in the chromosomal regions in which disease genes are found. Rodent orthologs associated with neurological function exhibit the greatest evolutionary conservation; this suggests that rodent models of human neurological disease are likely to most faithfully represent human disease processes. However, with regard to neurological triplet repeat expansion-associated human disease genes, the contraction, relative to human, of rodent trinucleotide repeats suggests that rodent loci may not achieve a 'critical repeat threshold' necessary to undergo spontaneous pathological repeat expansions. The identification of six genes in this study that have multiple characteristics associated with repeat expansion-disease genes raises the possibility that not all human loci capable of facilitating neurological disease by repeat expansion have as yet been identified.

Project description:The monofunctional penicillin-binding DD-peptidases and penicillin-hydrolyzing serine beta-lactamases diverged from a common ancestor by the acquisition of structural changes in the polypeptide chain while retaining the same folding, three-motif amino acid sequence signature, serine-assisted catalytic mechanism, and active-site topology. Fusion events gave rise to multimodular penicillin-binding proteins (PBPs). The acyl serine transferase penicillin-binding (PB) module possesses the three active-site defining motifs of the superfamily; it is linked to the carboxy end of a non-penicillin-binding (n-PB) module through a conserved fusion site; the two modules form a single polypeptide chain which folds on the exterior of the plasma membrane and is anchored by a transmembrane spanner; and the full-size PBPs cluster into two classes, A and B. In the class A PBPs, the n-PB modules are a continuum of diverging sequences; they possess a five-motif amino acid sequence signature, and conserved dicarboxylic amino acid residues are probably elements of the glycosyl transferase catalytic center. The PB modules fall into five subclasses: A1 and A2 in gram-negative bacteria and A3, A4, and A5 in gram-positive bacteria. The full-size class A PBPs combine the required enzymatic activities for peptidoglycan assembly from lipid-transported disaccharide-peptide units and almost certainly prescribe different, PB-module specific traits in peptidoglycan cross-linking. In the class B PBPs, the PB and n-PB modules cluster in a concerted manner. A PB module of subclass B2 or B3 is linked to an n-PB module of subclass B2 or B3 in gram-negative bacteria, and a PB module of subclass B1, B4, or B5 is linked to an n-PB module of subclass B1, B4, or B5 in gram-positive bacteria. Class B PBPs are involved in cell morphogenesis. The three motifs borne by the n-PB modules are probably sites for module-module interaction and the polypeptide stretches which extend between motifs 1 and 2 are sites for protein-protein interaction. The full-size class B PBPs are an assortment of orthologs and paralogs, which prescribe traits as complex as wall expansion and septum formation. PBPs of subclass B1 are unique to gram-positive bacteria. They are not essential, but they represent an important mechanism of resistance to penicillin among the enterococci and staphylococci. Natural evolution and PBP- and beta-lactamase-mediated resistance show that the ability of the catalytic centers to adapt their properties to new situations is limitless. Studies of the reaction pathways by using the methods of quantum chemistry suggest that resistance to penicillin is a road of no return.

Project description:BACKGROUND: Duplicated genes can indefinately persist in genomes if either both copies retain the original function due to dosage benefit (gene conservation), or one of the copies assumes a novel function (neofunctionalization), or both copies become required to perform the function previously accomplished by a single copy (subfunctionalization), or through a combination of these mechanisms. Different models of duplication retention imply different predictions about substitution rates in the coding portion of paralogs and about asymmetry of these rates. RESULTS: We analyse sequence evolution asymmetry in paralogs present in 12 Drosophila genomes using the nearest non-duplicated orthologous outgroup as a reference. Those paralogs present in D. melanogaster are analysed in conjunction with the asymmetry of expression rate and ubiquity and of segregating non-synonymous polymorphisms in the same paralogs. Paralogs accumulate substitutions, on average, faster than their nearest singleton orthologs. The distribution of paralogs' substitution rate asymmetry is overdispersed relative to that of orthologous clades, containing disproportionally more unusually symmetric and unusually asymmetric clades. We show that paralogs are more asymmetric in: a) clades orthologous to highly constrained singleton genes; b) genes with high expression level; c) genes with ubiquitous expression and d) non-tandem duplications. We further demonstrate that, in each asymmetrically evolving pair of paralogs, the faster evolving member of the pair tends to have lower average expression rate, lower expression uniformity and higher frequency of non-synonymous SNPs than its slower evolving counterpart. CONCLUSIONS: Our findings are consistent with the hypothesis that many duplications in Drosophila are retained despite stabilising selection being more relaxed in one of the paralogs than in the other, suggesting a widespread unfinished pseudogenization. This phenomenon is likely to make detection of neo- and subfunctionalization signatures difficult, as these models of duplication retention also predict asymmetries in substitution rates and expression profiles.

Dataset Information

Evolutionary rate analyses of orthologs and paralogs from 12 Drosophila genomes.

Publications

Evolutionary rate analyses of orthologs and paralogs from 12 Drosophila genomes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets