The masculinization of the X chromosome: many genes for early male sperm production reside on the X chromosome

In an entirely counterintuitive result, scientists have found that nearly half of all genes related to the earliest stages of sperm production reside not on the male sex (Y) chromosome as expected, but on the X chromosome, a chromosome universally thought of as the female sex chromosome.

The finding, published in the April issue of Nature Genetics, comes as a big surprise and is causing scientists to rethink the "gender identity" of the X chromosome.

"Scientists and non-scientists alike are comfortable thinking about the Y chromosome as a specialist in male characteristics. By default, weve traditionally thought of the X chromosome as sexually neutral or as a specialist in female characteristics. Our findings indicate that the X chromosome has a specialty in sperm production, much like the Y chromosome does," says David Page, lead author on the paper and a researcher at the Whitehead Institute for Biomedical Research and Howard Hughes Medical Institute.

The finding also raises the speculation that infertility due to low sperm production may be an X-linked disorder, passed on to male children through their mothers, much like color-blindness or hemophilia.

In this study, the Page lab researchers and their colleague John McCarrey at Southwest Foundation for Biomedical Research, in San Antonio, Texas, sought to study the genetic underpinnings of spermatogonia-stem cells in the testes that give rise to sperm. Spermatogonia are "the mother of all sperm cells," but unlike other stem cells, such as blood stem cells, which have been the subject of intense study, sperm stem cells have remained largely unexplored. So Jeremy Wang, a postdoctoral fellow in the Page lab, and his colleagues conducted a systematic search for genes that are active exclusively in sperm stem cells in mice.

The researchers found 25 genes, including 19 new ones, that were expressed exclusively in mouse sperm stem cells. They found that of these, only 3 were linked to the Y

Contact: Nadia Halim
Whitehead Institute for Biomedical Research

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