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Old 13-04-2007, 15:47   #3
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The rhesus macaque has become the third primate to have its genome fully sequenced, joining humans and chimpanzees.

The newly completed genome gives biologists a much deeper understanding of a crucial organism in biomedical research. It also offers evolutionary biologists a vantage point from which they can better understand the genetic changes that turned humans into such unusual apes.

An international consortium [http://www.hgsc.bcm.tmc.edu/projects/rmacaque/] of more than 170 scientists at 35 institutions sequenced the entire genome of a female macaque living at a research centre in San Antonio, Texas, US.

The macaque's nearly 3 billion DNA base pairs are 93.5% identical to those found in the human genome, as expected for a species whose lineage diverged from that of humans about 25 million years ago. By comparison, the human and chimp genomes, which diverged about six million years ago, are about 98% identical.

The rhesus macaque is already a valuable study organism for biomedical research, including drug testing and work on infectious diseases such as HIV and influenza. With genome in hand, biologists should now be able to refine their experiments by focusing on animals bearing particular genetic traits, thus gleaning more information from fewer animals, says Richard Gibbs, a geneticist at Baylor College of Medicine in Houston, Texas, who led the macaque sequencing consortium.

Resolving uncertainty

Having three genomes from closely related primate species also gives biologists much greater leverage in understanding primate evolution. Before, if the human and chimp versions of a gene differed, there was no way to know which of the two had been modified from the ancestral version.

Now, biologists can look to the macaque version to resolve the uncertainty. "We can take an unbiased look at what the genome is telling us needed to change," says David Haussler at the University of California at Santa Cruz in the US.

A genome-wide search turned up over 200 genes that appear to have evolved under natural selection in either the macaque or human-chimp lineages since the two diverged. Since these genes represent the levers by which evolution led humans to differ from macaques, researchers will be looking closely at them to help understand the evolution of modern humans.

Thinking caps

The gene list identified so far includes genes for hair structure, immune response, intercellular communication and sperm-egg fusion – but not, apparently, for brain size.

One puzzling discovery is that several mutations that cause genetic diseases in humans – such as phenylketonuria and Sanfillipo syndrome, which lead to mental retardation – are in fact the normal form found in macaques and, presumably, our own distant ancestors. "How can genes that seem to be fine in one species give disease in another closely related one?" asks Gibbs.

Such delicately balanced genes may be a good place to look for some of the key steps in the evolution of modern humans. Some cases of mental retardation, he speculates, may even result from mutations that return a key gene to its ancestral condition.

New Scientist
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