Human Y Chromosome Stays Intact While Chimp Y Loses Genes

While the human Y has maintained its count of roughly 27 genes andgene families over the last 6 million years, some of these same geneson the chimp Y have mutated and gradually become inactive. The authorsspeculate that one likely reason for such disparity is due tochimpanzee mating habits.

"Contrary to the dire predictions that have become popular overthe last decade, the sky is *not* falling on the Y," says WhiteheadMember and Howard Hughes Medical Institute investigator David Page,senior author on the study that will appear in the September 1 issue ofthe journal Nature. "This research clearly demonstrates that naturalselection has effectively preserved regions of the Y chromosome thathave no mechanisms with which to repair damaged genes."

For many years, it's been assumed that the Y chromosome isheaded for extinction because, unlike other chromosomes, it has nogenetic "mate" with which to swap genes. In 2003, Page published alandmark paper in Nature challenging that claim by demonstrating how acertain region of the Y chromosome possessed a unique mechanism forrepairing mutated genes.

Through sequencing the Y, the Page lab and collaborators atWashington University School of Medicine in St. Louis discovered thatmany of its genes were located in palindromes--long stretches of DNAletters that read the same forwards and backwards. By folding into ahairpin, the authors suggested, a gene might then swap the appropriategenetic material with itself. This demonstrated a process for the Ychromosome to maintain its integrity despite lacking a mate.

However, there is another region of the Y, called the "X-degenerate" region, where the genes are not situated in palindromes.

"The genes in the palindrome region are primarilysperm-producing genes, and most other genes unique to the Y aren'tlocated there," says Jennifer Hughes, a postdoctoral scientist inPage's lab and first author on the paper. These other genes have noobvious means for self-repair. Because of this, many proponents of the"Y's demise" theory remained undaunted.

Once again collaborating with Richard Wilson from theWashington University School of Medicine in St. Louis Missouri, Pageand his research team sequenced this X-degenerate region of thechimpanzee Y chromosome and compared it to the human Y.

"We were looking for any evidence that the human Y has lostgenes since parting ways with the chimp," says Hughes. "Had we foundactive genes on the chimp Y that had become inactive on the human, thatwould be the smoking gun. But we didn't find any such evidence. Infact, we found the opposite."

On the chimp Y, five genes have suffered mutations thatrendered them inactive. On the human Y, those same genes continue tofunction perfectly. "So then," says Hughes, "even though the Y has lostmany genes since its origin about 300 million years ago, it's beenholding steady in humans for the last 6 million years."

In other words, if the one region of the Y can depend on itself for survival, the other region has found a friend in evolution.

"We now see that natural selection *is* working to conserve thisunpartnered region of the Y," says Page, who is also a professor ofbiology at MIT. "If mutations do occur in any of these genes, theydon't seem to pass on in the lineage. This is a clear example of howevolution is not just about moving ahead, it's also about not fallingbehind."

Fortunately for the primate world, male chimps, just like malehumans, are probably not bound for early extinction. Those genes in theX-degenerate region are what scientists call "housekeeping" genes,meaning that they are active in most cells in the body and don't carryout any male-specific functions.

Page and his team speculate that the loss of genes on thechimpanzee Y may be due to the chimp's mating habits. Both male andfemale chimps engage with multiple partners when they mate. This givesa strong selective pressure on those genes that produce sperm.Conversely, it puts less pressure on evolution to preserve those geneson the Y whose functions have nothing to do with reproduction. Becausehumans historically have been largely monogamous, our Y chromosomeshave been spared such selective-pressure imbalance.

"Of course," acknowledges Page, "this is a hypothesis that wehave no way to scientifically prove or disprove. However, we believeit's currently the best explanation."

This work was supported by the National Institutes of Health and the Howard Hughes Medical Institute.