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Biomedicine

Fresh Insight into Evolution

Studies of genetic recombination suggest that genetic shuffling varies by gender.

It’s a tantalizing thought worthy of X-Men-inspired daydreams: are some of us, for better or for worse, evolving faster than others? Growing evidence suggests that rates of genetic recombination–one of the driving forces of human evolution–vary greatly between individuals. Two new studies shed further light on the inner workings of this gene-shuffling process, highlighting differences in the way men and women rearrange the DNA that they pass on to their children. The findings could help scientists understand disorders such as miscarriage and Down syndrome, which are linked to errors in recombination.

Genetic recombination: When cells divide to produce eggs and sperm, a process called meiosis, corresponding maternal and paternal chromosomes pair up and swap small pieces of DNA. (Paired chromosomes are depicted above.) This ensures a constant source of genetic diversity, which drives evolution.

During recombination, corresponding maternal and paternal chromosomes align within cells and swap bits of DNA. These cells eventually develop into sperm and eggs, endowing future offspring with a different configuration of genes than their parents. “Recombination constitutes one of the most powerful means by which new combinations of genetic variants are generated in the genome,” says Kari Stefansson, chief executive officer of deCODE Genetics, in Iceland, and senior author of one of the studies.

Previous research shows that recombination is often localized to specific spots on the genome, known as hot spots. Some people’s genomes undergo this swap more than other people’s, with apparently profound consequences. In 2005, Stefansson’s group at deCODE found that women with higher recombination rates had more children, suggesting that evolution has selected for molecular mechanisms that create diversity.

Scientists study recombination by comparing genetic variation in parents and their children. New techniques to analyze huge numbers of genetic variations, commonly used to identify genes linked to disease, are now allowing a more detailed analysis of recombination than ever before. (See “Genes for Several Common Diseases Found.”) In one such study, published Thursday in the online version of the journal Science, researchers from the University of Chicago generated a high-resolution map of recombination hot spots by analyzing the DNA of 725 people. The volunteers came from 82 families of Hutterites, a genetically similar group of European immigrants who settled in the Dakotas in the 19th century.

That map allowed researchers to analyze how specific hot spots varied between men and women, and parents and children. “Some individuals use some hot spots more than others,” says Graham Coop, a researcher at the University of Chicago who led the work. Coop and his collaborators also found that men and women had different recombination rates and tended to use different hot spots for recombination. In addition, that pattern of hot-spot usage seemed to be inherited. “That suggests differences in recombination machinery between indviduals,” says Coop. He ultimately hopes to identify the genes that control recombination.

Stefansson and his colleagues do just that in a second study, also published Thursday in Science. The researchers scanned the genomes of 20,000 people for specific genetic variations linked to recombination rate. They identified two variations within a gene known as RNF212 that together accounted for 22 percent and 6.5 percent of paternal and maternal variation, respectively. Little is known about the function of the gene.

Surprisingly, these variations had opposite effects in men and women: the mutation that increased recombination in women did the opposite in men, and vice versa. The findings suggest an evolutionary mechanism for keeping control of genetic diversity. “It’s important to increase diversity, but if it goes unchecked, it’s likely to lead to instability in the genome that could be dangerous,” says Stefansson. “If you have the same sequence variant influencing recombination in one direction in men and the other direction in women, you have put together a mechanism to keep recombination rates within certain limits.”

Both studies shed light on the basic underpinnings of human evolution, which could ultimately impact human health. For example, abnormal recombination can result in miscarriage. Older women, who have higher rates of miscarriage, tend to have children whose genomes show evidence of higher recombination rate. A better understanding of the mechanisms underlying this observation could eventually lead to new fertility treatments.

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