X-tra Diversity for Africans
Call it the X factor. Compared with Europeans and Asians, Africans have extra diversity on their X chromosomes, according to an invited lecture at the meeting by Cornell University geneticist Andrew Clark. The lack of diversity in non-Africans may be the legacy, handed down for thousands of generations, of fewer women than men in the bands of modern humans who first left Africa to colonize the rest of the world, Clark said.
His team used new data from the 1000 Genomes Project to resolve a recent debate about diversity on the X and to begin to explain why non-Africans have so little variation on this sex chromosome compared with the other chromosomes, or autosomes. “We're seeing a very consistent pattern of reduced X diversity out of Africa,” Clark said. “It shows a greater loss of variation than even in the autosomes out of Africa.”
To evolutionary geneticists, the X chromosome has always been something of a riddle. Unlike its partner the Y, the X still has its full complement of genes. But because of the way it is inherited—men inherit only one copy from their mothers, whereas women inherit a copy from each parent—the X is less diverse than autosomes in populations. So the chromosome has been a low priority for sequencers interested in disease risk, and published sequences have been of poor quality. But interest was piqued 3 years ago when teams studying frequencies of different alleles on the X got different results: One group found the X was less diverse in non-Africans, but another group didn't.
Then last year, the 1000 Genomes Project (Science, 29 October 2010, p. 574) posted its pilot data, including sequences of the complete genomes of 69 women from Africa and Europe. These data provide a much sharper view of the X, including single-nucleotide polymorphisms (SNPs). “The 1000 Genomes data rides to the rescue,” Clark quipped.
Researchers have long known that Africans have more diverse genomes overall, presumably because the small bands of ancestors traveling out of Africa passed through a genetic bottleneck and lost many variants. Cornell's Alon Keinan, Clark, and their colleagues devised a clever method to compare the amount of variation in SNPs on the X with that on the autosomes and applied it to 36 Yoruba women from West Africa. They found the X had about 73% of the diversity of the autosomes, as expected. But when Keinan examined the genomes of 33 European women, he found that their X chromosomes had only about 61% of the diversity of their autosomes. Because the European genomes were already less diverse overall, this extra effect meant that the Africans' X chromosomes were twice as diverse as those of the Europeans.
Because of the X's pattern of inheritance, the reduction in diversity out of Africa is likely due to some sex-linked demographic process, Keinan says. One likely explanation is that more men than women were members of the bands who moved out of Africa, a gender imbalance also seen on the front line of some other migrations.
Other researchers find the work convincing. “We are converging on an answer,” says computer scientist August Woerner, who works with geneticist Michael Hammer at the University of Arizona in Tucson. Hammer's lab was the one that saw more diversity on the X of non-Africans, but with whole genome sequences, they, too, have now found more diversity in Africans, resolving the debate. “The simplest explanation is waves of male migrations or a few males disproportionately passing on their X chromosomes” by having many children, says geneticist Joshua Akey of the University of Washington, Seattle.