Researchers have discovered that large portions of the X chromosome – long thought to be the “female” version of the male Y chromosome – have evolved to play a specialized role in sperm production.
The study, published in the journal Nature Genetics, reveals that although the X chromosome has a “reputation” of being the most stable chromosome of the genome, it has rapidly evolved.
Researchers from the Whitehead Institute say the results mean that the medical and biological importance of the X chromosome needs to be reevaluated.
David Page, director of the Whitehead Institute, Cambridge, MA, says:
“We view this as the double life of the X chromosome. The X is the most famous, most intensely studied chromosome in all of human genetics. And the story of the X has been the story of X-linked recessive diseases, such as color blindness, hemophilia, and Duchenne’s muscular dystrophy.”
“But there’s another side to the X, a side that is rapidly evolving and seems to be attuned to the reproductive needs of males.”
The study involved comparing the X chromosome in mice with that in humans in order to test how the “longstanding biological tenet” that the gene content of the X chromosome is shared and conserved across mammals, the researchers say.
This was done by using a unique sequencing method created by David Page along with developers at Washington University in St. Louis – single-haplotype iterative mapping and sequencing (SHIMS). This enabled the researchers to discover the human X reference sequence.
After then improving this reference sequencing, the researchers found that both the mouse and the human X chromosome have almost 95% of their “X-linked, single copy genes in common” and nearly all of these genes are expressed in both sexes.
The scientists say their most interesting discovery was finding 340 genes that were not shared between mice and humans. The researchers say that these genes seem to have developed by themselves over the 80 million years since humans and mice were separated from “common ancestors.”
When the researchers analyzed the expression of these genes, they found them to be almost exclusively active in the testicular germ cells, meaning that they are very likely to contribute to sperm production.
Jacob Mueller, a postdoctoral researcher at the Whitehead Institute, says that these genes are more likely to have roles in diseases that are related to reproduction such as infertility and testicular cancer.
“This is a collection of genes that has largely eluded medical geneticists. None of these genes have been associated with a Mendelian trait. Now that we are confident of the assembly and gene content of these highly repetitive regions on the X chromosome, we can start to dissect their biological significance.”