Human Gene Set Downsized

A proteomic analysis suggests a smaller number of protein-coding genes in the human genome.

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In order to confidently say

In order to confidently say that a gene is not ever expressed, one would have to subject the organism to every conceivable stress, like trauma, radiation, etc. The abstract for this study says simply this:

"...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."

I've not read the article in detail, but it appears that they used other evidence outside of proteomics, such as gene conservation, to further confirm that proteins not expressed under normal circumstances are not likely to be unexpressed under any circumstance. I find this approach of searching for "additional negative proof of expression" unconvincing. Negative proofs are always difficult if not impossible. When they start from a weak foundation, they are of little or no value in my opinion.

Clamp et al (PNAS 2007 vol.

Clamp et al (PNAS 2007 vol. 104, p. 19428) did a comprehensive analysis of protein-coding genes using annotated genes plus comparative genomics, with filters to identify ORFs likely to be statistical artifacts due to atypical codon usage. They came up with 20,470 for the human genome. This could probably be updated with more cDNAs, proteomics and more sequenced genomes, but is unlikely to be a gross overestimate. I agree that evidence of expression is good, but absence of evidence is necessary but not sufficient to conclude that a gene is not "real".

Non-coding RNAs do not

Non-coding RNAs do not produce peptides but still play major role in regulation of various biological functions in the body. Hope that will not be "filtered out"...

Amazingly, we still do not

Amazingly, we still do not have a reliable number of protein coding genes..
Michael Lerman, Ph.D., M.D.

Reminds me of the old debate

Reminds me of the old debate from the 70's using RNA-DNA hydridization experiments regarding high-complexity RNAs. Another regarding the 5000 genes in the fly versus the 20-30,000 or 100,000 estimated in humans we were looking for. I am guessing but it seems the complexity is in how the building blocks are actually used. Brain complexity comes from how many cell type connections, not how many cell types.

These gene's are just the paints/numbers of crayons in one's toolbox. Just because you have and may use 72 crayons doesn't mean your drawing is always going to be more complex than someone using say 20 crayons.