>>Previously, we noted how statistical tests
of natural selection were able to support
the idea that high infant mortality in the
Andes is being caused by high levels of arsenic.
This statistical test demonstrated that the
gene variant that metabolizes arsenic was
in such a high frequency that it could not
be explained by drift alone, thus implicating
natural selection. There are many examples
of how this population genetic approach to
natural selection has been used to understand
similar important traits, including adaptations
to high elevations, starch consumption, milk
consumption, HIV and other traits conferring
resistance to viruses and similar pathogens.
There are other examples that are less clear,
where we see unusual allele frequencies that
could be explained easily by natural selection
or genetic drift. One of my favorite examples
is a gene called aldehyde dehydrogenase 2.
A variant of this gene causes severe aversion
to alcohol. People with this trait get a very
strong flushing response in their cheeks after
drinking a small amount of alcohol, and most
will get physically ill even if attempting
to drink in moderation. This is because the
gene variant they carry, known as ALDH2-2,
is unable to metabolize alcohol normally.
Instead, acetaldehyde, a byproduct of alcohol
metabolism, builds up in their system rather
than being further broken down and removed
from their system. Acetaldehyde is toxic in
high levels. What's very odd about ALDH2-2
allele is that it's in very high frequency
in Asia, but nearly nonexistent everywhere
else in the world. Remember this is a very
odd pattern, because in humans typically if
a trait is common in one place in the world
it is typically common everywhere in the world.
So ALDH2 is a candidate for a gene undergoing
natural selection. The selective pressure
on ALDH2 is unclear. For one it's unlikely
to be alcoholism. I mean, somewhat facetiously,
alcohol often leads to reproduction rather
than limits it. Also the diseases associated
with alcoholism are typically late on-set,
such as cirrhosis of the liver, which often
happens after the most reproductively fruitful
period of life. Prevention of fetal alcohol
syndrome and similar fetal alcohol spectrum
disorders could be a candidate, given that
children with these disabilities are less
likely to be reproductively active. But these
disorders typically require high levels of
alcohol consumption by the mother. Importantly,
refined alcohols that we have today are a
relatively recent invention. And so it's not
a very compelling argument that these disorders
would be a major selective pressure explaining
ALDH2-2 allele.
Alternatively, one potential selective pressure
is parasites. Acetaldehyde is toxic to humans
at high doses, but it's also toxic to human
parasites, even at lower doses. It's possible
that ALDH2-2 allele provides resistance to
parasites, which could be a major selective
advantage. What makes this story even more
challenging is the age of the particular allele.
Using our understanding of the rates of genetic
mutation, we can use what's called a molecular
clock to estimate how old this particular
genetic trait is. ALDH2-2 is roughly 40,000
years old, around the same time as the peopling
of Asia. This means that the founder effect
leading to the peopling of Asia may have also
been responsible for the increased allele
frequency. In other words, in the case of
ALDH2 we don't need natural selection to come
up with a relatively reasonable explanation
for the -2 allele frequency. It could simply
be chance. Overall ALDH2-2 remains a bit of
a mystery. However, a related gene called
ADH2 also has some odd allele frequencies,
especially in Asia. So there's a lot to this
story that still needs to unfold.
