Multiple evidence strands suggest that there may be as few as 19 000 human protein-coding genes

被引:321
作者
Ezkurdia, Iakes [1 ]
Juan, David [3 ]
Manuel Rodriguez, Jose [4 ]
Frankish, Adam [5 ]
Diekhans, Mark [6 ]
Harrow, Jennifer [5 ]
Vazquez, Jesus [2 ]
Valencia, Alfonso [3 ,4 ]
Tress, Michael L. [3 ]
机构
[1] CNIC, Unidad Prote, Madrid 28029, Spain
[2] CNIC, Lab Prote Cardiovasc, Madrid 28029, Spain
[3] Spanish Natl Canc Res Ctr CNIO, Struct Biol & Bioinformat Programme, Madrid 28029, Spain
[4] Spanish Natl Canc Res Ctr CNIO, INB, Madrid 28029, Spain
[5] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England
[6] Univ Calif Santa Cruz, Sch Engn, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA
基金
美国国家卫生研究院;
关键词
PREDICTION; PROTEOMICS; DATABASE; GENOME; ANNOTATION; SEQUENCES; TOPOLOGY; ALGORITHM;
D O I
10.1093/hmg/ddu309
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 massspectrometry(MS) experiments. Here, we mapped peptides detected in seven large-scale proteomics studies to almost 60% of the protein-coding genes in the GENCODE annotation of the human genome. We found a strong relationship between detection in proteomics experiments and both gene family age and cross-species conservation. Most of the genes for which we detected peptides were highly conserved. We found peptides for >96% of genes that evolved before bilateria. At the opposite end of the scale, we identified almost no peptides for genes that have appeared since primates, for genes that did not have any protein-like features or for genes with poor cross-species conservation. These results motivated us to describe a set of 2001 potential non-coding genes based on features such as weak conservation, a lack of protein features, or ambiguous annotations from major databases, all of which correlated with low peptide detection across the seven experiments. We identified peptides for just 3% of these genes. We show that many of these genes behave more like non-coding genes than protein-coding genes and suggest that most are unlikely to code for proteins under normal circumstances. We believe that their inclusion in the human protein-coding gene catalogue should be revised as part of the ongoing human genome annotation effort.
引用
收藏
页码:5866 / 5878
页数:13
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