  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.
