What makes us human (genetically at least) take 2

The 28 April 2023 issue of Science has a fabulous collection of papers about the genomes of 240 species of mammals (out of 6,500 total).  Now remember that only 2% of our 3,200,000,000 basepair genome is involved in coding for the amino acids making up our proteins.  So when Genome Wide Association Studies come up with a region linked to a trait or a disease, 80% of the time it’s in the 98%.  This is where comparison of our genome with the 240 comes in so handy.  11% of our genome is the same as these other species (rather than the expected 1%).  These fall into 100,000,000 different sites.

The ENCODE study defined Cis-Regulatory Elements (CREs) as small regions of the genome with evidence of regulatory.  Many of them are binding sites for transcription factors.  Far far from all of them are evolutionarily conserved (e.g. are the same in all mammalian species studied).  This implies that these elements emerged at the beginning of the mammalian lineage.  They predominate near genes functioning in metabolism and development.  The work found 439,000 deeply conserved candidate CREs (cCREs) accounting for 4% of the human genome.

The most constrained CREs  are involved in mRNA processing and embryonic development.

One of the cleverest papers in the bunch (and which I never would have thought of doing) looked for genome sequences which have been conserved in mammals but which have been lost in man (these are called hCONDELs), some are over 1 kiloBases long, but 96% are much smaller (under 20 nucleotides).   Only 5% of 10,032 hCONDELs are in protein coding regions.  Many involve transcription transcription factor binding sites — obviously this is rewiring of the control  structure of cellular function and metabolism. Transcription binding sites aren’t very long (usually under 50 nucleotides) which is why even a hCONDEL of under 20 nucleotides can have such a major functional effect on them.   Remember what makes us different from other species isn’t our proteins (bricks) but the plan — for more on this please see   https://luysii.wordpress.com/2015/09/27/it-aint-the-bricks-its-the-plan/.   Even more interesting, 80/800 hCONDELs changed function only in neural precursors (of the 6 cell types studied).

There is tons more in the issue.  Find a copy and read it.  It shows that to really understand humans we have to look outside ourselves (and our genomes).

Next up — primate genomes.  But first wish us a happy 59th wedding anniversary,.