Practical Importance of Human Evolution – Genetics, Phylogenetics & Health – Natural Selection

Practical Importance of Human Evolution – Genetics, Phylogenetics & Health – Natural Selection


>>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.

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