The Y chromosome has long been thought of as a stagnant part of the genome, where genes are slowly decaying in males of all species. But the first comprehensive comparison of the Y chromosome in two species--specifically, humans and chimpanzees--shows that in fact, it is a hot spot of evolution. "It's really exciting; it's totally well-documented; it's really dramatic," says population geneticist Andrew Clark of Cornell University.
As is well-known, humans and chimps share 98% of their DNA. But more than 30% of the DNA differs between chimps and humans in the region of the Y chromosome that determines sex. This suggests that the Y chromosome has undergone "extraordinary" remodeling in both species in the 6 million years or so since they split from a common ancestor, says geneticist David Page, director of the Whitehead Institute of the Massachusetts Institute of Technology in Cambridge.
For almost a century, researchers have thought that the Y chromosome, with far fewer genes than the X, was decaying. Both sex chromosomes evolved from an ordinary pair of chromosomes more than 200 million years ago (Science, 29 October, 1999, p. 964). But since then, the Y has steadily lost genes as well as its ability to recombine and swap genes with the X chromosome. This suggested that the Y has long been an isolated chromosome with little left to lose--just a couple of hundred genes, at most, whose job is to produce sperm and determine the sex of offspring. As a result, researchers predicted that the Y chromosome should be nearly identical in humans and chimpanzees, like the rest of the genome.
Page and his collaborators set out to test this idea by sequencing the male-specific region of the Y (MSY) in both chimps and humans. Conventional shotgun sequencing methods can only be used for fairly short strands of DNA. The time-consuming but thorough sequencing of the entire chimp MSY has led to unexpected complexity.
When the team members compared the MSY sequences, they got a surprise. They found that the chimpanzee Y chromosome has lost lots of genes that are present in humans, which suggests the human Y resembles that of the common ancestor more than does the chimp's Y. Chimpanzees only have two-thirds of the genes present in the human MSY. But the chimpanzee MSY has acquired twice as many palindromes--large blocks of DNA in which the sequence of nucleotides is a mirror image of the sequence on its complementary strand. The addition of new palindromes in chimpanzees and humans has led to major structural differences in the Y of both species, the team reported online in Nature today. "The palindrome regions of the Y are almost like a house that is being rebuilt," says Page--one in which similar, prefabricated units are being added on in different ways in the genomes of the two species.
The researchers propose that the rapid evolution and wholesale remodeling of the Y chromosome in both species have been caused by several mechanisms, including the competitive advantage gained by developing new genes for sperm production. In chimps in particular, natural selection favors the production of lots of sperm because many males mate with fertile females, so males that produce more (or better) sperm have more offspring. The researchers also suggest that because the Y cannot exchange genes with the X chromosome anymore, it uses other unusual ways to reconfigure its DNA, such as recombining with itself to add on new segments of identical DNA--or palindromes--into its genome.
"Just when we thought we were getting the sense that we had a pretty good picture of what our genome is like and how it evolved, we get tossed this curve ball," says geneticist Huntington Willard of Duke University in Durham, North Carolina. "There are gems still buried in genomes that we haven't fully uncovered yet."