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Our lab has studied the genetic differences between males and females for decades.
Understanding those differences could show why certain conditions such as heart disease
or lupus are more common in one sex than another.
Many researchers study these sex biases by investigating one condition in detail.
We thought to take a completely different approach
to start not with the disease endpoints
but to simply assert that there must exist molecular differences between males and females
across the body, potentially in every cell type
and that coming to a basic and fundamental understanding of those molecular differences
would prove powerful
in the context of any sex-biased disease setting.
The researchers asked how gene expression differs between males and females throughout the body
including in the heart, skin, and brain.
So we looked at gene expression in 12 organs, in five different species
human, monkey, mouse, rat and dog really span much of the breadth of mammalian evolution.
They have a last common ancestor that lived about 80 or 100 million years ago.
Looking at this group of species would let the scientists know
whether the sex biases had evolved long ago or had arisen more recently in primates or in humans.
What really caught our eye was that we could find conserved sex-biased gene expression
in every organ we looked at
which is pretty exciting.
And at the same time, we found that the majority of the sex-biased gene expression
had evolved more recently.
One of the big next steps is to figure out, do these differences
in gene expression between the sexes—do they actually matter?
As a test case, the researchers looked at one of the most intensely studied genetic traits—height.
While the distributions of heights in males and females overlap,
there’s about a 13-centimeter difference in average height.
My graduate student Sahin Naqvi thought that perhaps conserved, sex-biased gene expression
might manifest, in part, in this larger height or size in males as compared to females.
In what was for us a very surprising, stunning, and exciting explanation
for 12% of the 13-centimeter shift.
This finding showed the researchers that the sex-biased gene expression can affect a male-female
difference in a trait.
It’s important because it validates the functional significance of the sex-biased
gene expression.
There are functional consequences.
We operate with a sort of unisex view of human biology
and I think that ignores the stark reality
that health and disease play out very differently
in XX and XY individuals.