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

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 (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.

1α,25-Dihydroxyvitamin D3 Regulates Mitochondrial Oxygen Consumption and Dynamics in Human Skeletal Muscle Cells

“…The altered mRNAs represent 10.2% of known protein coding genes in the human genome (68). The differentially expressed mRNAs encode proteins that play significant roles in multiple biochemical pathways involved in muscle contraction and relaxation; extracellular matrix-cell receptor interactions; actin cytoskeleton remodeling; and JAK-STAT, insulin-like (17) 0.014 Reactome p53 pathway (16) 0.014 Panther Interferon-signaling (11) 0.017 Panther Muscle contraction (9) 0.022 Reactome Terpenoid backbone biosynthesis (6) 0.028 KEGG Cell adhesion molecules (24) 0.048 KEGG (27), which showed that treatment of vitamin D-deficient humans with cholecalciferol improves muscle phosphocreatine recovery after exercise, suggesting an effect of 1␣,25(OH) 2 D 3 on the formation of high energy phosphorylated intermediates and mitochondrial function.…”

The Spatial Homeostasis Hypothesis

“…Therefore, it can be assumed that the carrier of hereditary information is not so much the primary sequence of nucleotides in DNA, but rather the spatial or "holographic" organization of the whole DNA molecule (including its non-coding part, which constitutes up to 98%) [61,62], which is unique to each organism and is defined by the primary structure.…”

Transcriptome Analysis for Non-Model Organism: Current Status and Best-Practices

“…LncRNAs are RNA molecules that are longer than 200 nucleotides in length and do not contain protein-encoding sequences. Recent studies have shown that although human genome contains about 19,000 protein-encoding genes (approximately 2% of the genome) [88], 58,684 high-quality lncRNAs have been identiied in the genome using a large-scale transcriptome analysis [89]. Accumulating evidence showed that the protein-coding genes are accounted for only 50% of inal assembled transcriptome data.…”