Re: Amylase gene locus in humans

On 9/7/2024 8:24 AM, Athel Cornish-Bowden wrote:

On 2024-09-06 17:00:52 +0000, RonO said:
 

https://www.nature.com/articles/s41586-024-07911-1
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https://www.sciencedaily.com/releases/2024/09/240904141503.htm
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There is a new paper on the genetic variation of the amylase gene locus in humans.  Humans and great apes have 3 amylase genes (AMY1, AMY2A, and AMY2B).  Primates started out with one amylase gene and were insectavores.  Monkeys had an altered diet and were mainly frugivores (fruit-eating) and have 2 copies of the amylase gene (AMY1 and AMY2). A second duplication occurred in the common ancestor of great apes to produce the 3 copies that many humans still have.  Further duplications occurred in the evolution of modern humans.  This paper indicates that Homo had 3 genes until around 238,000 years ago when another duplication event occurred.  There have been multiple duplication and rearrangements of the multigene locus since.  Around 12,000 years ago several different gene amplification events were selected for likely due to the increase in grains in the agricultural diet.  The locus now has inverted repeats and direct repeats with some haplotypes with 20 copies of amylase genes instead of the original 3.  One major duplication contains 2 inverted repeats that are duplicated as direct repeats.  This sequence contains 4 amylase genes and is around 100 kb in length.  As noted this 100 kb sequence is itself duplicated in some haplotypes as a direct repeat.
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They have identified the rapid evolution of copy number of the various haplotypes.  This is due to the fact that abberrant recombination between misaligned direct repeats produce one chromosome with fewer copies and the other chromosome with more copies.  100 kb is around 1/10th of a centiMorgan, so 1 in a thousand meiotic events have a chance at misaligning the direct repeats and causing loss and gain of copies of the repeat due to recombination.  This would occur at a much higher frequency than the original duplication mutations, and accounts for the rapid evolution in copy number that is now going on within the human population.  Recombination between an inverted sequence and the ancestral orientation is usually lethal.  Inversions are associated with decreased recombination, but it isn't all due to misalignment, but if recombinantion does occur it results in very large deletions of one arm or the other of a chromosome and is usually lethal.  Recombination between inverted repeats on the same chromosome causes inversion of the sequence between the inverted repeats, so they can cause additional inversions.
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So what they have found is a boat load of different copy number haplotypes with higher copy number haplotypes selected for in agricultural populations.
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They note that the amplifications started before we started farming, but it has been known for a long time that most of the calories are acquired by the gatherers and not the hunters of hunter-gatherer groups.

 I "suffer" from amyloidosis (but "suffer" is a misleading term, and I wouldn't know I had it if an echographic test ordered by my cardiologist ordered hadn't said so). The name suggests it has something to do with carbohydrates, but it hasn't; instead it's a deposit on the heart of a denatured _protein_, erythropoietin. I'm taking an incredibly expensive (7300€ per month) drug called tafamidis (sold as Vyndaqel), fortunately not paid by me). It doesn't cure amyloidosis but it stops it getting worse.
 

The first guy to identify the protein plaques mistakenly thought that they were starch granules.  So now we call the protein plagues, like those associated with Alzheimer's, amyloid plagues.
Even inappropriate names have presidence.
Ron Okimoto