Researchers Find Surprising Difference Between Human and Chimp Genomes

Cambridge, Mass., Thursday, February 10, 2005 – In today's online version of the journal Science , researchers report a surprising find: Despite 99% similarity at the level of DNA sequence between humans and our nearest relative, chimpanzees, the locations of DNA swapping between chromosomes, known as recombination hotspots, are nearly entirely different.

This difference is intriguing because one of the central tenets of modern biology is that specific DNA sequences determine biological function. In most cases, when DNA sequence is highly similar between two species, the biological function of that DNA is predictably similar as well.

The international research team consists of collaborating investigators from the Broad Institute of MIT and Harvard; Massachusetts General Hospital (MGH); Harvard Medical School (HMS); the University of Oxford, UK; and the Biomedical Primate Research Centre, Netherlands.

Recombination 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. Recently it was discovered that recombination does not occur at random across the human genome, but rather is localized to particular places in the genome called "hotspots."

Because these hotspots are very important to studying genetic disease in humans, the research team set out to compare recombination in the genomes of humans and chimpanzees. They expected that the patterns would 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.

In their paper, which will be published online by the journal Science at the Science Express web site February 10, the researchers report that:

* Although the DNA sequence of the two species is nearly identical, recombination hotspots were rarely, if ever, found at the same positions.
* Local patterns of recombination rate have evolved rapidly, in a manner disproportionate to the change in DNA sequence.

"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," 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 MGH and HMS. "However, progress was stymied because identifying hotspots was laborious and inefficient."

Fortuitously, Altshuler and Peter Donnelly, a professor of statistics at the University of Oxford, were co-chairing the analysis of the International Haplotype Map project (www.hapmap.org), a public project to map human genetic variation for use in disease research. Donnelly's laboratory had recently developed a statistical method that allowed recombination rates to be studied on a genomic scale. "We shared our ideas at a HapMap conference, and after discussions, teamed up with the Boston group for this study. It ended up being a very close collaboration, with daily contact, even though we were 3,000 miles away," said Donnelly, who is co-senior author on the paper.

Working together, the research team analyzed data collected in Boston with the methods developed in Oxford and was able to identify 18 hotspots in human and three hotspots in chimp. To their surprise, none of the hotspots occurred in the same locations in human and chimp.