NEWS NATURE|Vol 446|19 April 2007

Make way for monkeys

Rhesus macaques can’t claim the distinction of being humanity’s closest cousins, nor of ever having been popularized by Jane Goodall. But the newly completed analysis of the macaque’s genome could prove just as important as that of the chimpanzee’s, scientists say. Macaca mulatta is the third primate genome to be sequenced, following those for humans (Homo sapiens) and chimpanzees (Pan trog- lodytes). Adding the macaque to that picture, LIBRARY PICTURE B. CASTELEIN/NATURE scientists say, should allow researchers to make better sense of the other two genomes. And because the rhesus macaque is the main mon- key model for many diseases, understanding its genome could help to clarify why some dis- eases develop, and why some treatments work differently in monkeys from in humans. The macaque genome, published on 13 April in Science, is crucial for unravelling the evolu- tionary events that led to humanity. Ever since scientists released the chimp genome sequence in 2005 (see Nature 437, 69–87; 2005), they Analysis of the macaque genome could lead to improved models for diseases. have been busily trying to dissect how it differs from our own — looking for clues to explain The new analysis finds that where humans “A lot of people use macaques as a model for uniquely human traits. and macaques share genes, the DNA sequences the immune response, so the fact there are But when a genetic difference is identified in those genes are 97.5% identical. But the find- these differences is important,” says Evan Eich- between humans and chimps, it is not always ings also highlight differences between the spe- ler of the University of Washington in Seattle, possible to tell which form of the DNA is older. cies’ DNA. For instance, the scientists report one of the leaders of the analysis portion of the Scientists can compare each sequence to those that the 108 gene families shared between macaque project. of distantly related animals, such as chickens humans, macaques and chimps have evolved And that, scientists say, means that the and mice, but this technique fails when the differently in the three species, and about 60% macaque genome should be analysed in even genetic variant is so new that it is unique to of those amplified in the macaque show signs more detail. The current publication is only a primates. The macaque is therefore an ideal of natural selection. Some of these genes prob- ‘draft’ sequence — meaning it is not as com- reference point, scientists say, because the ably explain differences between humans and plete as, for instance, the human genome. evolutionary split between monkeys and apes monkeys — like our inability to swing through (such as humans and chimps) occurred 25 mil- forest treetops and our revulsion to ingesting Historical hangovers lion years ago, much earlier than the human– our own vomit. But already, plenty of material is available to chimp divergence 6 million years ago. The differences might also shed light on chew on. For instance, the analysis turned “Now that we have a third more medical issues. Macaques up hundreds of cases in which humans and primate, a large part of the “Understanding the are often used as stand-ins for macaques share a gene, but although the focus is understanding the changes in each primate humans in experimental tests macaque version keeps the monkey healthy, changes that happened in lineage is very important of drugs and medical treat- the human one causes disease. Understand- each primate lineage, and ments — especially for infec- ing the implications of this finding could take that is very important in in understanding tious diseases, such as HIV. some time. But it may cause some scientists to understanding evolution,” evolution.” But these monkey tests do not rethink their approach to the nature of disease. says George Weinstock of always accurately predict how Rather than being a recent glitch in our physi- the Baylor College of Medicine in Houston, the treatments behave in the human body. ology, a disease-causing gene might actually Texas, a leader of the macaque sequencing The new analysis finds that macaques have be a holdover from our ancestral history that effort. The project involved researchers from many more copies of genes corresponding to hasn’t kept pace with the way our bodies or North America, Asia and Europe (Rhesus those making up the human HLA system — a lifestyles have evolved, and has now become Macaque Genome Sequencing and Analysis key part of the body’s defence against diseases. detrimental. Consortium Science 316, 222–234; 2007). Finding that the HLA system is genetically “We tend to think about disease very sim- And the macaques could soon have company. different in macaques could be a sign that the plistically, that everything was fine until a new Other primate genome sequences in progress monkeys’ immune systems don’t work like our variant was introduced, and then things went include the gibbon (Nomascus leucogenys), own. That information, in turn, could help awry,” Weinstock says. “But actually, it is much orangutan (Pongo pygmaeus), gorilla (Gorilla researchers design more accurate preclinical more complex than that.” ■ gorilla) and marmoset (Callithrix jacchus). tests in macaques. Erika Check

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