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The shrinking human protein coding complement: are there now fewer than 20,000 genes?

Iakes Ezkurdia, David Juan, Jose Manuel Rodriguez, Adam Frankish, Mark Diekhans, Jennifer Harrow, Jesus Vazquez, Alfonso Valencia, Michael L. Tress
doi: https://doi.org/10.1101/001909
Iakes Ezkurdia
1Unidad de Proteómica, Centro Nacional de Investigaciones Cardiovasculares, CNIC, Melchor Fernández Almagro, 3, rid, 28029, MadSpain
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David Juan
2Structural Biology and Bioinformatics Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro, 3, 28029, Madrid, Spain
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Jose Manuel Rodriguez
3National Bioinformatics Institute (INB), Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro, 3, 28029, Madrid, Spain
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Adam Frankish
4Wellcome Trust Sanger Institute, Wellcome Trust Campus, Hinxton, Cambridge CB10 1SA, UK
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Mark Diekhans
5Center for Biomolecular Science and Engineering, School of Engineering, University of California Santa Cruz (UCSC), 1156 High Street, Santa Cruz, CA 95064, USA
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Jennifer Harrow
4Wellcome Trust Sanger Institute, Wellcome Trust Campus, Hinxton, Cambridge CB10 1SA, UK
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Jesus Vazquez
6Laboratorio de Proteómica Cardiovascular, Centro Nacional de Investigaciones Cardiovasculares, CNIC, Melchor Fernández Almagro, 3, 28029, Madrid, Spain
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Alfonso Valencia
2Structural Biology and Bioinformatics Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro, 3, 28029, Madrid, Spain
3National Bioinformatics Institute (INB), Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro, 3, 28029, Madrid, Spain
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Michael L. Tress
2Structural Biology and Bioinformatics Programme, Spanish National Cancer Research Centre (CNIO), Melchor Fernández Almagro, 3, 28029, Madrid, Spain
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Abstract

Determining the full complement of protein-coding genes is a key goal of genome annotation. The most powerful approach for confirming protein coding potential is the detection of cellular protein expression through peptide mass spectrometry experiments. Here we map the peptides detected in 7 large-scale proteomics studies to almost 60% of the protein coding genes in the GENCODE annotation the human genome. We find that conservation across vertebrate species and the age of the gene family are key indicators of whether a peptide will be detected in proteomics experiments. We find peptides for most highly conserved genes and for practically all genes that evolved before bilateria. At the same time there is almost no evidence of protein expression for genes that have appeared since primates, or for genes that do not have any protein-like features or cross-species conservation. We identify 19 non-protein-like features such as weak conservation, no protein features or ambiguous annotations in major databases that are indicators of low peptide detection rates. We use these features to describe a set of 2,001 genes that are potentially non-coding, and show that many of these genes behave more like non-coding genes than protein-coding genes. We detect peptides for just 3% of these genes. We suggest that many of these 2,001 genes do not code for proteins under normal circumstances and that they should not be included in the human protein coding gene catalogue. These potential non-coding genes will be revised as part of the ongoing human genome annotation effort.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC Unported 3.0 license.
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Posted January 17, 2014.
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The shrinking human protein coding complement: are there now fewer than 20,000 genes?
Iakes Ezkurdia, David Juan, Jose Manuel Rodriguez, Adam Frankish, Mark Diekhans, Jennifer Harrow, Jesus Vazquez, Alfonso Valencia, Michael L. Tress
bioRxiv 001909; doi: https://doi.org/10.1101/001909
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The shrinking human protein coding complement: are there now fewer than 20,000 genes?
Iakes Ezkurdia, David Juan, Jose Manuel Rodriguez, Adam Frankish, Mark Diekhans, Jennifer Harrow, Jesus Vazquez, Alfonso Valencia, Michael L. Tress
bioRxiv 001909; doi: https://doi.org/10.1101/001909

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