Detlev Arendt, Tobias Doerks, Peer Bork, Christopher J. Creevey, Jean Muller, Julie D. Thompson, Animal & Grassland Research and Innovation Centre, Teagasc - The Agriculture and Food Development Authority (Teagasc), European Molecular Biology Laboratory [Heidelberg] (EMBL), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de diagnostic génétique, CHU Strasbourg, Max-Delbrück-Centre for Molecular Medicine, This work was funded by the EURASNET grant (European Union FP6 Programme, Contract number LSH-2004-1.1.5-3)(http://www.eurasnet.info/). CJC wishes to acknowledge current support from the Science Foundation Ireland (SFI) Stokes Lectureship Programme (Reference number: 07/SK/B1236A)(http://www.sfi.ie), European Project: 32894,EURASNET, European Union, Science Foundation Ireland, LSH-2004-1.1.5-3, 07/SK/B1236A, Autard, Delphine, and European Alternative Splicing Network of Excellence - EURASNET - 32894 - OLD
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., Author Summary The correct identification of single copy (1-to-1) orthologs is crucial for functional classification of genes and for phylogenetic studies of groups of organisms, including the Metazoa. Nevertheless, despite the recent increase in the number of genomes and short sequence read datasets (e.g. ESTs) from the Metazoa, we know little about their completeness and how useful they may be for phylogenetic studies. Here we describe a novel approach for the identification of single copy gene families at any hierarchical level and demonstrate its effectiveness by identifying a set of over one thousand gene families that have been in single copy since the last common ancestor of the Metazoa. By comparing our orthologs to those predicted by other datasets we show that our procedure identifies a significantly larger set of single copy orthologs in the Metazoa. We then use this dataset to assess 24 metazoan genomes and 61 metazoan EST datasets for their completeness. We thus identify the underlying error rate in genome annotation and suggest a mechanism for assessing the quality of genomes and EST datasets in terms of their suitability for phylogenetic studies.