The X Chromosome Behind Every Man

The case of the month is an actual patient of The Turek Clinic.
He was just an ordinary guy minding his own business. Until he tried to have kids and found out that he was sterile. No sperm. Not a speck. When I asked him what struck him first when he was told that he was azoospermic, he shrugged his shoulders. No idea. A perfect citizen. When I looked for the known causes of azoospermia, I shrugged my shoulders. Clean as a whistle. He had a normal Y chromosome and a normal chromosomal constitution.

The Inimitable Y Chromosome

The human genome probably holds 20,000 to 30,000 genes. It is thought that over 1000 genes control human male infertility. We know about 20-30 of them at the moment.  Nice try, I know. Our gentleman could easily have a genetic issue that we simply don’t know about.
The Y chromosome, the true home of human maleness, is the obvious place to look for infertility genes. Truth is, we know a lot about this chromosome and they are not all there. Of course, several other really important genes live there, including (and I am kidding):

  • Air Guitar gene
  • Inability to Hear/See Obvious gene
  • Male Answer Syndrome gene
  • Channel Flipping gene
  • Pseudo Self-Confidence gene
  • Rock Throwing gene
  • Vehicular Attraction gene
  • Refusal to Ask For Directions gene

The X Chromosome in Men

Given this, I dare you to now guess which chromosome is the most likely place where a big chunk of male fertility genes live. That’s right. The freakin’ X chromosome!
Very recent and very well performed science now suggests that the X chromosome is leading a “double life:” it tends to the needs of both women and men. An earlier suggestion of this came 10 years ago from mouse studies looking at early germ cells (spermatogonia) that eventually develop into sperm. Among new genes identified in early male germ cells, more were derived from the X chromosome than the Y chromosome. Although several of these are known, including the FATE gene and SOX-3, none are currently testable.

But Why?

Why would the X chromosome have male fertility genes on it? Who knows. But thinking teleologically, the following may make some sense:

  • Reproductive fitness is important to preservation of a species
  • Protecting reproductive genes increases reproductive fitness
  • Keeping reproductive genes on the Y or X chromosomes are better places than elsewhere in the genome to protect them (increased meiotic drive).
  • Since the Y chromosome is relatively fragile placing critical male fertility genes on the more stable X chromosome (“backup”) makes good evolutionary sense.

As the old proverb says: “Behind every great man is a woman (rolling her eyes).”