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

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 t