Priming the Human Primate
|Progression from fangs to teeth, low-brow to high|
Researchers have learned that despite the 99 percent similarity between the DNA of humans and our closest relative, the chimpanzee, a significant difference occurs in the places along the genome where gene swapping occurs.
In the Feb. 10 online issue of the journal Science, researchers from the Broad Institute of MIT and Harvard report with colleagues that the locations of DNA swapping between chromosomes, known as recombination "hotspots," are nearly entirely different.
"We started trying to compare recombination in humans and chimpanzees a couple of years ago, in the hope that better understanding this fundamental mechanism might inform our approach to mapping genes for human diseases, but our progress was stymied because identifying hotspots was laborious and inefficient," said co-senior author Dr. David Altshuler, director of the Broad’s program in Medical and Population Genetics and associate professor of genetics and of medicine at Massachusetts General Hospital and Harvard Medical School.
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Recombination–or the swapping of genes between chromosomes–shapes the patterns of genetic variation in a species. It is the process in which DNA from an individual’s father and mother is reshuffled to create new combinations of genes in the child–new combinations on which natural selection can act to shape the evolution of the species.
Scientists recently discovered that recombination does not occur at random across the human genome, but is localized to particular places in the genome called hotspots. Because these hotspots are important to the study of genetic disease, the research team set out to compare recombination in the genomes of humans and chimpanzees. They expected the patterns to be very similar between the species, and that by comparing the DNA it would be possible to identify particular DNA sequences that might explain the localization of recombination to hotpots.
The research team analyzed data collected in Boston using the methods developed in Oxford that make it possible to survey recombination at a genomic scale. They identified 18 hotspots in humans and three hotspots in chimps. To their surprise, none of the hotspots occurred in the same locations in human and chimp.
|Evolutionary branches of the primate species depicted on the tree. Full image.
Credit: Mark A. Klingler, Carnegie Museum of Natural History
"The surprising conclusion seems to be that there is probably something other than the DNA sequence, or perhaps in addition to it, that is determining where these hotspots are located," said Altshuler. "Epigenetic factors–biological codes that are layered on top of the DNA–may turn out to be more different in closely related species than the DNA sequence itself."
In addition to the Broad researchers, the international research team consists of investigators from Massachusetts General Hospital (MGH), Harvard Medical School (HMS), the University of Oxford, and the Biomedical Primate Research Centre in the Netherlands. Authors on the study are Broad researchers Stacey Gabriel, Robert Onofrio, Daniel Richter, and Wendy Winkler (of Broad and MGH); Gavin McDonald and David Reich of Broad and HMS; Simon Myers and Gilean McVean from the University of Oxford; and Ronald Bontrop from the Biomedical Primate Research Centre in the Netherlands.
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