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Text A. How Our Genomes Control Diversity

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Two research efforts have determined DNA recombination mechanisms that underlie population diversity, how it happens and where in the genetic code it occurs

By Nikhil Swaminathan

Two recent discoveries have shed new light on the source of diversity in the human population. In one study, scientists examined patterns in DNA recombination, the process by which a person's genome is consolidated into one set of chromosomes to pass onto an offspring. In the other, a link was made between variants of a particular gene and the extent to which DNA recombination occurs.

In human testes and ovaries, where sperm cells and egg cells, respectively, are manufactured, sections of chromosomes inherited from a person's parents are shuffled together to create a collage of genetic material that is passed to offspring. This process by which a new, unique set of chromosomes is created (with a mix of roughly half the material coming from each parent) is called DNA recombination and is the source of variation in populations. "Recombination impacts population diversity," says George Coop, a postdoctoral fellow in human genetics at the University of Chicago and co-author of an article that details variation in the pattern in which genes are shuffled from individual to individual. "Recombination is the way that you generate novel haplotypes, novel combinations of mutations." (Haplotypes are combinations of different versions of genes on a single chromosome that are inherited as a unit.)

Coop and colleagues in Science reveal the results of a high-resolution study designed to map the locations where recombination occurs—where one parent's genes have been swapped out for another. Using a population of 725 Hutterites—communal farmers who settled in the Dakotas and Montana in the mid-19th century—the team scanned genomes for 500,000 single-nucleotide polymorphisms (SNPs). SNPs mark points of genetic variation to estimate where DNA shuffles occurred. Researchers can tell which part of a child's genetic code came from which of its four grandparents by comparing variants in both.

The researchers noted nearly 25,000 total recombination events in analyses of 364 offspring. Excluding the sex chromosomes, the team found that eggs typically showed 40 instances of recombination on each of their chromosomes, whereas the chromosomes in sperm are typically made with 26 recombinational occurrences. The University of Chicago team also noted that as women age, more recombination takes place during meiosis (the cellular process that produces an egg). In men, there is no age effect. Further, they noted that such incidents tended to focus on so-called "hot spots," locations where this crossover takes place often. Some turned out to be gender specific, with females utilizing some recombination regions more often than males (and vice versa). The usage of these zones of frequent recombination varied between individuals, but it seemed to be conserved among families, indicating that the extent and pattern of recombination may be inherited.

Interestingly, a finding out of the Icelandic biotech firm deCODE genetics, also appearing in Science, sheds light on that last observation. From a genome-wide analysis looking at 300,000 SNPs in 20,000 people, deCODE scientists were able to find two locations on a gene found on chromosome 4 and link variations at those two locales to the recombination rate. "What's interesting about the SNPs is that the variants have opposite effects on the sexes," says deCODE's chief executive officer Kari Stefansson. According to the new study, one of the locations on the gene, known as RNF212, is associated with high rates of recombination in men, but low rates in women; for the other marker, the gender effect is reversed. "If you were going to design a mechanism to keep rates within [certain] limits you would do exactly this," Stefansson explains about the gender paradigm. "For one generation, it leads to higher recombination rate; for the next generation, it would lead to a lower recombination rate." Overall, the two positions can account for 22 percent of the variability in a man's recombination rate and 6.5 percent of the variability in a female's, the study says.

Chicago's Coop lauded the deCODE efforts, noting that this was the first mapping of a gene that influences recombination in mammals. "I would imagine that the variation that we see in individuals is in part caused by these SNPs," he says. "I think this represents a big step forward in determining the events of human recombination." (From Scientific American Online, February 5, 2008)


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