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Monkey Business

By Kevin Davies

Oct 17, 2005 | Thirty years ago, a young Ph.D. and her supervisor published a landmark paper in Science [1]. By today’s big biology standards, the methodologies were a joke. Nevertheless, using a rudimentary combination of protein electrophoresis and DNA hybridization experiments, Mary-Claire King and Allan Wilson deduced that humans and chimps are 99 percent identical at the protein level. They concluded: “A relatively small number of genetic changes in systems controlling the expression of genes may account for the major organismal differences between humans and chimpanzees.”

Thanks to the international chimpanzee genome consortium [2], scientists are finally able to confirm and extend the Berkeley duo’s predictions. The sequence of Clint, a male chimpanzee, comprising 18 chromosomes and 2.8 billion bases, was assembled by the groups of Bob Waterston (University of Washington), Richard Wilson (Washington University in St. Louis), and Eric Lander (Broad Institute).

Although humans and chimpanzees last shared a common ancestor six million years ago, biologists have long been struck by the striking physiological and behavioral similarities between the species. Indeed, the Swedish taxonomist Carl Linnaeus originally classified the chimpanzee in the genus Homo, before it was renamed Pan troglodytes.

That relatedness is borne out beautifully at the DNA level. The degree of divergence between the two sequences is a mere 1.23 percent, or 35 million single nucleotide polymorphisms. Almost one-third of the chimpanzee genes are identical to their human counterparts. The actual gross difference in genomes is closer to 3 percent, however, as a result of about 5 million DNA insertions and deletions.

With apologies to devotees of the honeybee, wallaby, and a few other organisms of specialized interest, the chimpanzee warrants special attention because of the widespread belief that comparative scrutiny of the sequence differences between the two species will reveal clues as to what makes humans “special.” Can discrete genetic alterations be tied to traits such as the development of language, bipedalism, hirsutism (or lack thereof), brain size, and so on? Put another way, why are humans able to celebrate sequencing the chimp genome, and not the other way round?

“We now have a nearly complete catalogue of the genetic changes that occurred during the evolution of the modern human and chimpanzee species from our common ancestor,” says the Broad Institute’s Tarjei Mikkelsen. “By cross-referencing this catalogue against clinical observations and other biological data, we can begin to identify the specific changes that underlie the unique traits of the human species.”

A logical place to start is with a group of 585 genes that show evidence for “positive selection” — they have accumulated more substitutions than expected by chance. One of the best examples is the FOXP2 gene, mutations in which severely affect language development in humans. The consortium also notes six haplotypes — blocks of conserved DNA — that have swept through the human genome. Their significance is not yet understood, but intriguing mutations have been identified in genes linked to Alzheimer’s disease and inflammation.

But as King and Wilson suggested, we must also compare the expression, not just the raw sequences, of human and chimpanzee genes. In a survey of five tissues by Svante Paabo and colleagues [3], the greatest activity differences were found in the liver, with the fewest, surprisingly, in the brain. The authors conclude that structural and regulatory changes have acted in concert during evolution.

Clearly the search for clues using comparative genomics and other techniques is just beginning. Part of the problem is that chimps and humans are just too good a match. Thus, there will be almost as much interest in the upcoming draft sequences of the marmoset, macaque, and orangutan, and work to sequence the gorilla genome is about to get under way.

The impact of the chimpanzee genome is not confined to science. It offers an urgent reminder of the endangered status of many primate species. The recent Kinshasa agreement on primate conservation is a useful step in the right direction, but continued vigilance is essential. Man’s respect for and generosity to his fellow man has been found wanting of late. Let us hope that our more distant cousins do not have cause to feel so hopelessly abandoned.

1          King, M.-C. and Wilson, A. Science 188, 107-116 (1975).
2          The Chimpanzee Sequencing and Analysis Consortium. Nature 437, 69-87 (2005).
3           Khaitovich, P. et al. Science 309, 1850-1854 (2005).

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