The X and Y chromosomes determine sex in the human population. Females are characterized by having two X chromosomes (XX), while males have one X and one Y chromosome (XY). The X chromosome is larger than the Y chromosome, containing approximately 1,100 to 1,500 genes that play crucial roles in developing various organs in the human body. The X chromosome can be inherited from both parents, whereas the Y chromosome can only be passed down from the father. The Y chromosome, though smaller, is responsible for male traits and attributes like the development of testes and gonads. Compared to the X chromosome, the Y chromosome only contains 50 to 200 genes, which are primarily involved in developing the male reproductive system.

According to various studies, including research by Jennifer A. Marshall Graves, the Y chromosome has shrunk from 1,438 genes to only 45. It is predicted that in the next 11 million years, the Y chromosome may disappear entirely, potentially leading to the extinction of males and endangering human survival.

Why is the Y chromosome important? The Y chromosome carries the Sex-determining Region Y (SRY) gene, which is responsible for developing the male reproductive system, including the testes. Despite being smaller, the Y chromosome plays a vital role in human evolution and survival.

In hopes of addressing this issue, the Proceedings of the National Academy of Sciences conducted research on the Amami spiny rat, a rodent species from Japan that has lost its Y chromosome and evolved a new male-determining gene. Studying how this species adapted could provide insights into how similar mechanisms might be applied to humans.

The study, led by Asato Kuroiwa at Hokkaido University, involved six individuals from the Amami spiny rat population (three males and three females). This sample was used for genomic resequencing and analysis to identify sex-specific genomic regions. The study employed various techniques, including genomic sequencing, SNP analysis, CNV analysis, Hi-C analysis, and statistical methods. A total of 83,451 candidate sex-associated SNPs (Single Nucleotide Polymorphisms) and 41 candidate sex-associated CNV (Copy Number Variant) regions were identified. A small duplication near the SOX9 gene on chromosome 3 was found in male spiny rats but not in females. This duplication activates the SOX9 gene, leading to the development of male reproductive organs. The findings suggest that the turnover of sex chromosomes in the Amami spiny rat is linked to the loss of the Y chromosome and the emergence of new sex-determining mechanisms.

One of the significant findings from the study is that the duplicated region near the SOX9 gene is located on topologically associated domains (TADs) in male spiny rat cells. TADs are segments of DNA that interact more frequently with each other than with other regions, playing a crucial role in gene regulation. The duplicated region's location within the SOX9 TAD suggests that it has the potential to make chromatin interactions with the SOX9 gene, further supporting its role in male sex determination. This discovery sheds light on how the spiny rat's genome has adapted to compensate for the loss of the Y chromosome, potentially offering insights into the evolutionary mechanisms that could occur in humans if the Y chromosome were to disappear.

However, the study's limitations include the small sample size, which may restrict the generalizability of the findings, and the focus on a single species, which may not fully represent the complexities of sex chromosome evolution across different mammalian species. Moreover, the Amami spiny rat is an endangered species, heavily protected by the Japanese government, which presents challenges for conducting further genetic studies. Despite these limitations, the research provides a unique opportunity to explore the early stages of sex chromosome turnover in mammals, particularly in a species that has already lost its Y chromosome and SRY gene.

Based on this research, there is a possibility that humans could also evolve a new sex-determining gene and continue to survive in the absence of the Y chromosome, offering hope for the future. The identification of the duplicated SOX9 enhancer in the spiny rat opens the door to investigating whether similar mechanisms could be harnessed or engineered in humans. If successful, this could prevent the potential extinction of males and ensure the continuation of the human species.

However, like two sides of a coin, there is also a potential downside to this evolution. Scientists have cautioned that the presence of multiple sex-determining systems in the human population could lead to the emergence of entirely new species, each with different biological mechanisms. The discovery that different enhancers can independently regulate SOX9 expression adds complexity to our understanding of sex determination and highlights the potential for diverse evolutionary pathways.

The SRY gene, discovered in 1990, was found to activate the SOX9 gene, which, although not located on the Y chromosome, plays an active role in developing male reproductive organs. The absence of the Y chromosome would lead to the loss of the SRY gene and, consequently, the lack of SOX9 gene activation. This has sparked debate among scientists; some believe the Y chromosome will persist and avoid extinction, while others predict its eventual disappearance. One thing is certain: there is hope, as species like the mole vole and the spiny rat have managed to evolve without the Y chromosome, suggesting that humans could also find a new way to ensure the survival of the male species. However, the emergence of new sex-determining systems could lead to increased genetic diversity, which might result in conflict between different sex genes, potentially leading to catastrophic events, as seen in mole voles and spiny rats.

Either way, the extinction of the Y chromosome would profoundly change the human population, potentially leading to the emergence of new species. However, the discovery of alternative mechanisms to develop male species brings a new ray of hope for the future of humanity​

Reference :

1. Terao, M., Ogawa, Y., Takada, S., Kajitani, R., Okuno, M., Mochimaru, Y., Matsuoka, K., Itoh, T., Toyoda, A., Kono, T., Jogahara, T., Mizushima, S., & 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 Sciences, 119(49). https://doi.org/10.1073/pnas.2211574119

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(Rehash/Yash Kamble/MSM)