Dataset Information

Identifying single copy orthologs in Metazoa.

ABSTRACT: The identification of single copy (1-to-1) orthologs in any group of organisms is important for functional classification and phylogenetic studies. The Metazoa are no exception, but only recently has there been a wide-enough distribution of taxa with sufficiently high quality sequenced genomes to gain confidence in the wide-spread single copy status of a gene.Here, we present a phylogenetic approach for identifying overlooked single copy orthologs from multigene families and apply it to the Metazoa. Using 18 sequenced metazoan genomes of high quality we identified a robust set of 1,126 orthologous groups that have been retained in single copy since the last common ancestor of Metazoa. We found that the use of the phylogenetic procedure increased the number of single copy orthologs found by over a third more than standard taxon-count approaches. The orthologs represented a wide range of functional categories, expression profiles and levels of divergence.To demonstrate the value of our set of single copy orthologs, we used them to assess the completeness of 24 currently published metazoan genomes and 62 EST datasets. We found that the annotated genes in published genomes vary in coverage from 79% (Ciona intestinalis) to 99.8% (human) with an average of 92%, suggesting a value for the underlying error rate in genome annotation, and a strategy for identifying single copy orthologs in larger datasets. In contrast, the vast majority of EST datasets with no corresponding genome sequence available are largely under-sampled and probably do not accurately represent the actual genomic complement of the organisms from which they are derived.

SUBMITTER: Creevey CJ

PROVIDER: S-EPMC3228760 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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Identifying single copy orthologs in Metazoa.

Creevey Christopher J CJ Muller Jean J Doerks Tobias T Thompson Julie D JD Arendt Detlev D Bork Peer P

PLoS computational biology 20111201 12

The identification of single copy (1-to-1) orthologs in any group of organisms is important for functional classification and phylogenetic studies. The Metazoa are no exception, but only recently has there been a wide-enough distribution of taxa with sufficiently high quality sequenced genomes to gain confidence in the wide-spread single copy status of a gene.Here, we present a phylogenetic approach for identifying overlooked single copy orthologs from multigene families and apply it to the Meta ...[more]

PMID: 22144877

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Project description:Copy-number variation (CNV), rather than complete loss of gene function, is increasingly implicated in human disease. Moreover, gene dosage is recognised as important in tumourigenesis, and there is an increasing realisation that CNVs may not be just symptomatic of the cancerous state but may, in fact, be causative. However, the identification of CNV-related phenotypes for mammalian genes is a slow process, due to the technical difficulty of constructing deletion mutants. Using the genome-wide deletion library for the model eukaryote, Saccharomyces cerevisiae, we have identified genes (termed haploproficient, HP) which, when one copy is deleted from a diploid cell, result in an increased rate of proliferation. Since haploproficiency under nutrient-sufficient conditions is a novel phenotype, we sought here to characterise a subset of the yeast haploproficient genes which seem particularly relevant to human cancers.We show that, for a subset of HP genes, heterozygous deletion is sufficient to cause aberrant cell cycling and altered rates of apoptosis, phenotypes associated with cancer in mammalian cells. A majority of these yeast genes are the orthologs of mammalian cancer genes, and hence our studies suggest that CNV of these oncogenic orthologs may be sufficient to lead to tumourigenesis in human cells. Moreover, where not already implicated, this cluster of cancer-like phenotypes in this model eukaryote may be predictive of the involvement in cancer of the mammalian orthologs of these yeast HP genes. Using the yeast set as a model, we show that the response to a range of anti-cancer drugs is strongly dependent on gene dosage, such that intermediate concentrations of the drugs can actually increase a mutant's growth rate.The exploitation of data on the phenotypic impact of heterozygosis in Saccharomyces cerevisiae has permitted the prediction of CNVs affecting tumourigenesis in humans. Our yeast data also suggest that the identification of CNVs in tumour cells may assist both the selection of anti-cancer drugs and the dosages at which they should be administered if they are to be a beneficial, rather than a deleterious, therapy.

Dataset Information

Identifying single copy orthologs in Metazoa.

Publications

Identifying single copy orthologs in Metazoa.

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