Not only are Y chromosomes relatively small, they also show surprisingly low levels of genetic diversity. So is the Y chromosome genetically indolent, destined to fade away, towing its diminishing horde of unimportant genes to oblivion? On the contrary: According to a new genetic analysis, the lack of variation exhibited by the Y chromosome reflects intense natural selection—a winnowing process that has removed harmful mutations. In this process, the Y chromosome has been pared down to its essentials. The Y chromosome, it appears, is here to stay, since natural selection is acting to maintain its gene content, much of which has been shown to play a role in male fertility.

This finding emerged from a comparison of Y chromosomes in eight African and eight European men. The comparison, conducted by scientists at UC-Berkeley, revealed patterns of variation that challenged common expectations.

“Y chromosomes are more similar to each other than we expect,” said Melissa A. Wilson Sayres, Ph.D., who led the new analysis. “There has been some debate about whether this is because there are fewer males contributing to the next generation, or whether natural selection is acting to remove variation.”

The scientists described how they explored these possibilities in a paper published January 9 in PLOS Genetics, in an article entitled “Natural Selection Reduced Diversity on Human Y Chromosomes.” As the title indicates, the authors found that a kind of purifying selection best explained the Y chromosome’s pattern of variation.

In summarizing their findings, the authors wrote: “Because there is no recombination across most of the Y chromosome all sites on the Y are effectively linked together. Thus, selection acting on any one site will affect all sites on the Y indirectly. Here, studying the X, Y, autosomal and mitochondrial DNA, in combination with population genetic simulations, we show that low observed Y chromosome variability is consistent with models of purifying selection removing deleterious mutations and linked variation, although positive selection may also be acting.”

The researchers found that all 27 genes on the Y chromosome—the 17 that humans retain after 200 million years of evolutionary history, and 10 more recently acquired but poorly understood genes—are likely affected by natural selection. Most of the newer genes, called ampliconic genes, are present in multiple copies on the chromosome, and loss of one or more copies has been linked to male infertility.

“These ampliconic regions that we haven’t really understood until now are evidently very important and probably should be investigated and studied for fertility,” said Dr. Wilson Sayres.

Dr. Wilson Sayres was able to precisely measure Y variability because for the first time she compared variation on a person’s Y chromosome with variation on that person’s other 22 chromosomes (called autosomes), the X chromosome and the mitochondrial DNA. She used whole genome data from 16 men whose DNA had been sequenced by the Mountain View-based company Complete Genomics.

Cross-population studies of variation in the Y chromosome are in their infancy, she said, noting that of the more than 36 mammalian genomes sequenced to date, complete Y chromosomes are only available for three. Most of the 1,000+ human genomes already sequenced do not have sufficiently accurate coverage of the Y to make this type of comparison among individuals, but advances in technology to better characterize DNA will facilitate future analyses of the Y chromosome, she said.

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