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Thursday, Sept. 8, 2005

NATURAL SELECTIONS

SEQUENCING SUCCESS

Could chimp genome answer Plato's question?


In the 1960s, Toshisada Nishida, of Kyoto University, set up a long-term research project in the Mahale Mountains of Tanzania. His aim was to study our closest relatives in the wild. His work, and that of Jane Goodall, whose field site was some 170 km north, in Gombe, transformed the way we view chimps.

Now, with completion last week of the chimp genome sequence, our view will again change.

A chimp called Clint, who died last year, supplied the DNA used to do the sequencing. He lived at the Yerkes National Primate Research Center in Atlanta, Georgia.

Clint's first legacy will be a change in the traditional view, cited in textbooks worldwide, that there is a 1.2 percent difference in the DNA of chimps and humans. Because of newly discovered duplications of DNA in the chimp genome, the difference is more like 2.7 percent. This means that the recognized number of genetic differences between humans and chimps is now approximately 60 times less than the differences between humans and mice, and about 10 times less than those between mice and rats.

On the other hand, the number of genetic differences between humans and chimps is about 10 times more than between any two humans.

You might say, "so what?" -- but knowing how we differ is important in evolutionary terms.

For example, DNA duplications allow natural selection more room to "experiment" with mutations that could give rise to new traits. On the flip side, they can lead to some two dozen genetic diseases.

"Now we need to learn the role of those duplication events in species evolution and disease," said Evan Eichler, of the Howard Hughes Medical Institute at the University of Washington School of Medicine.

"We know that there are some disease 'architectures' that are shared between chimp and human, so we know that is the ancestral state. But other predisposing structures have arisen only in the human lineage, so such comparisons can provide important information on the genetic histories of disorders and disease susceptibilities of the human species."

Eichler now wants to work out which of the genes in the duplications show the signatures of natural selection.

"This is a big question, because our hypothesis is that the big differences in structure between humans and chimps arose, or might be tolerated, because of important adaptations in the genes themselves."

In other words, we will be able to use the chimp genome to answer questions about how and why we differ from chimps.

It's an ancient question. Plato asked the same thing, without success.

Until Nishida and Goodall's work in the 1960s, it was thought that the ability to use tools was the characteristic that distinguished us from other apes. But then this idea, too, was trashed.

Next it was thought that language ability was what set us apart. But then chimps were taught to communicate with American sign language.

Hmm. OK, so then that changed to the current position, which is that we have syntax in our language, while chimps don't. But don't hold your breath. Only now can we really look at the differences and perhaps answer the question: What makes us human?

An immediately promising region of investigation will be that containing the FOXP2 gene. This has been implicated in the acquisition of speech in humans. So, as usual, much of the excitement about this chimp research is egotistic. It's exciting because it's going to tell us about ourselves.

But it really is exciting, because by comparing the human genome with the chimp's we will have an unparalleled method for understanding our own biology.

Since the ancestors of humans and chimps diverged, about 5 million years ago, there has been rapid genetic change in both species. The most important differences have occurred in genes involved in reproduction, the sense of smell and the immune system -- all of which are also areas of rapid change for other mammals.

Initial comparisons suggest that the greater complexity and larger size of the human brain compared to the chimp brain is less down to the development of new human genes for brain proteins than to changes in the way existing genes are used as the human brain develops.

But what will it tell us about chimps? Chimps are fascinating precisely because they are so similar to us. In the United States, in research institutions, sanctuaries and zoos, as well as in private homes and in the entertainment industry, there are some 2,000 West African chimpanzees. It is time, say scientists at the University of California, San Diego, to draw up ethical and scientific guidelines to protect their welfare.

Now their genome has been sequenced, there is likely to be an increase in research. And in the excitement, it must not be forgotten that conservation efforts are needed like never before. A report last week showed that a combination of logging, poaching for bush-meat and Ebola outbreaks are severely threatening chimps (and gorillas) in West Africa.

The San Diego scientists, writing in the journal Nature, which published the genome, said: "We urge all scientists studying great apes to contribute not only to the care of captive apes, but also to develop mechanisms by which studies of captive great apes would help generate a revenue stream to enhance support for the conservation of great ape populations in the wild."

A book of Natural Selections columns translated into Japanese, "Nou to sekkusu no seibutsugaku (Evolution, Sex and the Brain)," is published by Shinchosha. Rowan Hooper is a biologist at Trinity College, Dublin. He welcomes readers' comments at rowan.hooper@tcd.ie


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