Genetic mutation raises interesting questions about the evolution of the Y chromosome

The names and dates comprising a family tree contain branches that can extend backward centuries in time. People use these diagrams to discover their ancestral origin. Scientists use them to study the genealogical origins of entire species, tracing evolutionary history down to changes in a single gene.

Biologist Steve Rozen has explored the family tree of the male-determining Y chromosome, looking for information about a genetic mutation that raises interesting questions about the evolution of the Y.

Large genetic deletions of all or most of a region of the Y chromosome called the Azoospermia Factor c region almost always cause poor sperm production, and the variation is usually passed from father to son only through in vitro fertilization. It’s a rare mutation, affecting only about one in 4,000 men.

But Rozen and others in the lab of Whitehead Member and MIT professor David Page have discovered a new deletion in the same region. This deletion doesn’t always cause infertility, so it can be passed from father to son through normal reproduction. The deletion is therefore far more common in the general population; it may affect about 2 percent of all men in the United States.

While the discovery, reported in the journal Nature Genetics, offers new information about male infertility, it raises even more questions about the evolution of the Y. Though this deletion doesn’t always affect fertility, somewhere along the line, some men who inherit the deletion will be left with poor sperm production. The deletion should get weeded out. That’s how human evolution works.

But when Rozen began to investigate the deletion’s genealogical origin, he and his colleagues found one population where this mutation is thriving – Japan.

The Y’s genealogical chart is vast and while the finer branches are just now being discovered, the major limbs already tell the stories of Y chromosome variants that arose tens of thousands of years ago in different parts of the world. The scientists looked for evidence of chromosomes containing this particular deletion, and found this type of Y amidst others on 14 different branches of the chromosome’s family tree, including one where every single Y chromosome had the deletion. The scientists traced the geographical origin of this particular branch to Japan and discovered that 30 percent of all Japanese men have this chromosomal type.

“On the one hand, we have evidence that this deletion is being weeded out, somewhat slowly, but being weeded out nonetheless, because on average, the men with this deletion are at greater risk of having sperm production problems,” Rozen observes. “But on the other hand, we have a case where a branch with this particular deletion has gone to a very high frequency in one population. It’s contradictory and we don’t know how to resolve the contradiction.”

The scientists hope they won’t be stumped for long. The next step of their work will involve further analysis of this new deletion to unlock more secrets of this family tree.