New Sex Gene for Men? Y-chromosomes are disappearing

The Y chromosome is responsible for determining whether a human baby will be male or female. However, the Y chromosome in humans is degenerating and may disappear in a few million years. This could lead to our extinction unless we evolve a new sex gene. But there’s good news – two branches of rodents have already lost their Y chromosome and have survived.

In humans, females have two X chromosomes, while males have one X and one Y chromosome. The X chromosome contains about 900 genes that do various jobs unrelated to sex. In contrast, the Y chromosome has only 55 genes and a lot of non-coding DNA that doesn’t seem to do anything. However, the Y chromosome contains an essential gene called SRY that initiates male development in the embryo.

This master sex gene works by starting a genetic pathway that leads to the development of testes. The embryonic testes produce male hormones that ensure the baby develops as a boy. SRY triggers a gene called SOX9, which is key for male determination in all vertebrates, although it does not lie on sex chromosomes.

Read More: Women are More at Risk of Autoimmune Disease Than Men Due to The Presence of X Chromosome

Most mammals have an X and Y chromosome similar to humans. However, this system creates problems because of the unequal dosage of X genes in males and females. The platypus has completely different sex chromosomes, more like those of birds. This suggests that the mammal X and Y were an ordinary pair of chromosomes not that long ago. However, the Y chromosome has lost 900-55 active genes over the 166 million years that humans and platypuses have been evolving separately. At this rate, the last 55 genes will disappear in 11 million years.

The good news is we know of two rodent lineages that have already lost their Y chromosome and are still surviving. The mole voles of Eastern Europe and the spiny rats of Japan have some species in which the Y chromosome and SRY have completely disappeared. Although it’s not yet clear how the mole voles determine sex without the SRY gene, a team led by Hokkaido University biologist Asato Kuroiwa has had more luck with the spiny rat. Kuroiwa’s team discovered most of the genes on the Y of spiny rats had been relocated to other chromosomes. But she found no sign of SRY, nor the gene that substitutes for it.

In 2022, Kuroiwa’s team published a successful identification in PNAS. They discovered a tiny difference near the essential sex gene SOX9, on chromosome 3 of the spiny rat. A small duplication, present in all males and no females, was found. They suggest this small bit of duplicated DNA contains the switch that normally turns on SOX9 in response to SRY. When they introduced this duplication into mice, they found that it boosts SOX9 activity, so the change could allow SOX9 to work without SRY.

The disappearance of the human Y chromosome has elicited speculation about our future. To reproduce, we need sperm and men, meaning that the end of the Y chromosome could lead to the extinction of the human race. But the new finding supports an alternative possibility – that humans can evolve a new sex determining gene. However, the evolution of a new sex determining gene comes with risks. What if more than one new system evolves in different parts of the world? A “war” of the sex genes could lead to the separation of new species, which is exactly what has happened with mole voles and spiny rats.

This news is a creative derivative product from articles published in famous peer-reviewed journals and Govt reports:

1. Graves, J. (2022, December 5). Men are slowly losing their Y chromosome, but a new sex gene discovery in spiny rats brings hope for humanity. The Conversation.
2. Terao, M., Ogawa, Y., Takada, S., Kajitani, R., Okuno, M., Mochimaru, Y., … & Kuroiwa, A. (2022). Turnover of mammal sex chromosomes in the Sry-deficient Amami spiny rat is due to male-specific upregulation of Sox9. Proceedings of the National Academy of Sciences119(49), e2211574119.
3. Y. Zhan et al., Reciprocal insulation analysis of Hi-C data shows that TADs represent a functionally but not structurally privileged scale in the hierarchical folding of chromosomes. Genome Res. 27, 479–490 (2017).
4. Y. Ogawa et al., Mapping of a responsible region for sex reversal upstream of Sox9 by production of mice with serial deletion in a genomic locus. Sci. Rep. 8, 17514 (2018).
5. B. Croft et al., Human sex reversal is caused by duplication or deletion of core enhancers upstream of SOX9. Nat. Commun. 9, 5319 (2018).

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