Amylase gene locus in humans

[RonO]

https://www.nature.com/articles/s41586-024-07911-1

https://www.sciencedaily.com/releases/2024/09/240904141503.htm

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.

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.

So what they have found is a boat load of different copy number
haplotypes with higher copy number haplotypes selected for in
agricultural populations.

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.

Ron Okimoto

[Athel Cornish-Bowden]

Post by RonO
https://www.nature.com/articles/s41586-024-07911-1
https://www.sciencedaily.com/releases/2024/09/240904141503.htm
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.
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.
So what they have found is a boat load of different copy number
haplotypes with higher copy number haplotypes selected for in
agricultural populations.
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.

[RonO]

Post by Athel Cornish-Bowden

Post by RonO
https://www.nature.com/articles/s41586-024-07911-1
https://www.sciencedaily.com/releases/2024/09/240904141503.htm
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.
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.
So what they have found is a boat load of different copy number
haplotypes with higher copy number haplotypes selected for in
agricultural populations.
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