Y Not The X?

Imagine Louis Armstrong bellowing: “Birds do it, bees do it, goldfish in the privacy of bowls do it…” Males and females, everywhere on earth, falling for each other. Now there’s evidence that, even chromosomally, they need each other.

Sex Dogma

Realize that scientific thought surrounding sex chromosomes has been a tad sexist to date: Two Xs make a girl, and one Y makes a boy. Ok, news flash: in many organisms, including grasshoppers and crickets, maleness exists without a Y chromosome. There are even perfectly healthy (but infertile) men with two X chromosomes and no Y chromosome. So, as you may know already, sex is complicated.
We’ve known for some time that the Y chromosome lives a lonely life since it first split off of the X chromosome at least a hundred million years ago. During the genetic “swap meet” called cell replication, while other chromosomes pair up and exchange genes, the Y does not. Instead, it pairs with itself through odd chromosomal contortions. Typical male behavior, you might say.
Despite this strange behavior, or maybe because of it, the diminutive Y chromosome, smallest of them all, still packs a punch. It contains almost 80 known genes, many of which are crucial for building testicles and sperm. And we all know how important these are to keeping the species going. But over the millennia, the Y chromosome has also lost a pile of genes, estimated to be 97% of the total number it started with. That is very unlike the X chromosome, which has retained 98% of its genes, numbering about 1000.

Gone But Not Forgotten

So where have the Y-residing genes gone over time? Some are likely lost for good; after all, who needs gills or a tail anymore? Others, we now know are still around, but they have found new homes on other chromosomes. So, in travelling light, the Y chromosome has enlisted the help of other chromosomes to keep crucial genes alive.
What tickles me even more is that even important male fertility genes, identity-defining for any self-respecting Y chromosome, have relocated during evolution. And guess which chromosome probably contains the most male fertility genes other than the Y? You guessed it, the maternal X chromosome! There we go, cleaning up after him again, this time for his genomic mess!

Curse or Blessing?

Although we suspected this from rodent studies, a good friend and colleague, Alex Yatsenko at UPitt, recently showed the presence of a human sperm depriving, azoospermia-inducing gene mutation (Tex11) right smack on the X chromosome.
So from where would an infertile guy get his X chromosome mutation? Clearly, it would be passed to him from his mother (as Dads only pass Y chromosomes to sons). But, since most newly generated mutations are paternal in origin, maybe she just passed on a mutation that was given to her. In fact, the researchers suspect that these X mutations in infertile men may be derived from maternal grandfathers! Yup, add fertility to baldness when you look at your grandparents.
So what are the messages for Men’s Health Month? Well, it appears that it takes a chromosomal village to raise a man. And, as a corollary, do not judge a man simply by the Y chromosome he keeps.