`Female` X chromosome key contributor to sperm production
Washington: Scientists have found that large portions of the X chromosome -long perceived as the "female" counterpart to the male-associated Y chromosome - have evolved to play a specialized role in production of sperm.
This surprising finding is paired with another unexpected outcome: despite its reputation as the most stable chromosome of the genome, the X has actually been undergoing relatively swift change.
Taken together, these results suggest that it`s time to re-examine the biological and medical importance of the X chromosome.
Whitehead Institute Director David Page, whose lab conducted this latest research, said that the team is viewing this as the double life of the X chromosome.
He said that the X is the most famous, most intensely studied chromosome in all of human genetics, asserting that the story of the X has been the story of X-linked recessive diseases, such as color blindness, hemophilia, and Duchenne`s muscular dystrophy.
Page said that there is another side to the X, a side that is rapidly evolving and seems to be attuned to the reproductive needs of males.
Page`s lab embarked on a rigorous comparison of the mouse and human X chromosomes, in part to test the longstanding biological tenet that the gene content of X chromosomes is conserved and shared across mammals.
However, to render such a comparison valid, the lab had to upgrade the human X reference sequence, which was originally assembled as a mosaic of sequences from the X chromosomes of at least 16 people.
This composite left the reference with errors and gaps that fail to capture so-called ampliconic regions containing segments of nucleotides that are virtually identical. Such near-complete identity prevents recognition of tiny but important differences.
To set the sequence straight, the lab turned to the unique sequencing method Page had developed with collaborators at Washington University in St. Louis to help navigate the structural complexities of the Y chromosome .
Using single-haplotype iterative mapping and sequencing (SHIMS), the lab greatly improved the human X reference sequence, accurately assembling three large amplicons, identifying previously unknown palindromes, and ultimately shortening the entire length of the sequence by eliminating four major gaps.
Upgraded reference in hand, the lab discovered that, as might have been expected, the mouse and human X chromosomes have nearly 95 percent of their X-linked, single-copy genes in common. Almost all of these genes are expressed in both sexes. Strikingly, however, the lab identified approximately 340 genes that are not shared between the two species.
Fittingly, most of these genes reside in ampliconic regions of the X and appear to have been acquired independently during the 80 million years since mouse and human diverged from a common ancestor. Expression analyses revealed that these genes are active almost exclusively in testicular germ cells, where, at a minimum, they likely contribute to sperm production.
The paper has been published online in the journal Nature Genetics.
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