The Y chromosome is degrading. What does it mean for us?

by: Becky Dong


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What is the difference between a man and a woman? Genetically speaking, an X and a Y. At first glance, it’s merely a singular chromosome out of twenty-three pairs with different genetic material- until you notice how small the Y chromosome is to the X. It is hypothesized that the X and Y chromosomes were once paralogs, homologous genes with large chunks of the same genetic material that diverged due to genetic duplication, with sex chromosomes in placental mammals originating 180 million years ago, when the Y-linked gene responsible for male testis development (SRY) diverged from the X-linked gene SOX3. By chance, the Y chromosome accumulated large inversions that ultimately stopped most of the recombination with the X chromosome, which resulted in the immense gene loss seen today. Without recombination, errors and deletions build up, creating what scientists call a “genetic wasteland” filled with numerous repeats yet very few genes. Genetic destitution sounds terrifying, but what does it mean for the future of the Y chromosome?

Y chromosome theories

With such little material, it’s a miracle that the Y chromosome still exists, and scientists are still gauging how it survived against all odds. This has been addressed with three main hypotheses: the dominant Y, the selfish Y, and the wimpy Y. The dominant Y hypothesis posits that the Y chromosome simply carries the sex-determining genes needed for testes formation. Y chromosome domination can be seen in Klinefelter syndrome, in which the individual still presents as male despite carrying two X chromosomes in addition to a Y chromosome. In mammalian males, the X chromosome is almost wholly silenced to allow for gene dosage balance that allows the Y chromosome to express the gene needed for testis formation, TDF. Next is the selfish Y hypothesis, in which the Y accumulates genes beneficial for male development at the detriment of females, eliciting selfish growth factors that enhance Y chromosome survival. This would result in the Y chromosome exclusively carrying genes indispensable in male reproduction. Last but most likely is the wimpy Y hypothesis in which the Y is merely a relic of its former self, rife with unnecessary repeats and extremely gene-poor. The Y chromosome was thought to have once been equivalent in size to the X chromosome; now, it contains less than 10% of the genetic material of the X chromosome, making it a “wimpy” shell of its former genetic potential.

Is it here to stay?

There has been a heated debate regarding the human Y chromosome and whether the decline in genetic material would eventually lead to a purge of the Y chromosome. Some researchers believe that the continuous deterioration of the Y chromosome will lead to an inevitable end, but the fact that the SRY region of the Y chromosome, which hosts the male determining genes, cannot recombine hints at a mechanism for gene preservation. Research by Dr. Jenn Hughes argues that the Y chromosome has not experienced enough change to elicit substantial worry. Her lab compared the gene content of humans and chimpanzee male-specific Y sequences and determined that there was no gene loss from the human side in the past 6 million years when humans and chimpanzees diverged; hinting that gene loss is not constant as predicted by linear decay. Nature has clearly discovered numerous genetic tricks to outsmart the predicted decay of the Y chromosome.

The dangers of the Y chromosome

On average, women live longer than men. You might attribute this to the increased propensity for riskier behaviour, which can easily be seen from the barrage of foolish stunts posted on social media, but it may also be genetic. Studies from UCLA and Duke University have shown the relationship between testosterone and an increase in risk tolerance and a shift in impulsivity, but aside from that,  the lack of genetic material may attenuate one’s lifespan due to mosaic loss of the Y chromosome as one ages. As the Y chromosome is so small, the quantity of genetic material gradually declines with cell division, making it susceptible to mosaic loss, meaning that with age, males will slowly accumulate somatic cells lacking in Y chromosomes. The loss of genetic material comes with the potential for a lot of damage. For example, a study from Goethe University found that Y chromosome aneuploidy, the abnormal number of chromosomes caused by the loss of Y chromosomes, in myeloid cells originating from bone marrow promoted cardiac fibrosis in older men. They found that bone marrow–derived myeloid cells exhibited loss of the Y chromosome, which led to organ fibrosis caused by an increase in profibrotic macrophages with high transforming growth factor b1 (TGFb1), leading to fibrotic myocardium and heart failure. Although the effects of mosaicism aren’t well understood yet, this loss of genetic material is undeniably detrimental to man.

Although the Y chromosome is deteriorating, it seems like it won’t vanish anytime soon. But just because it’s here to stay doesn’t mean it doesn’t come with any risks. The Y chromosome may be a harbinger of doom, showing the risks that come with aneuploidy and lack of recombination. And while it pulls clever tricks to maintain function, it hasn’t been quick enough to evade the dangers of gene loss and repeat accumulation. It’s fascinating to see such a small chromosome hold so much influence over the cellular function of an entire organism and how much is lost in the process of protecting the male development genes hidden in the SRY region. So, will the wimpy Y steer itself away from obsolescence, or will it succumb to its genetically poor demise? 

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