A small step from monkey to the giant that is mankind

May 26, 2000

Why do humans get Aids and chimps don't? Some researchers say a chimp genome project would give us the answer. Ayala Ochert reports

Just this month, Human Genome Project scientists announced the completion of the entire sequence of chromosome 21. In the next couple of months, they expect to have a first working draft of the whole genome.

As this sequencing effort pushes ahead, we should soon find out what it means to be human at a genetic level. But will we?

Probably not, says Edwin McConkey, a molecular biologist at the University of Colorado. "In principle, there is a genetic basis for being human, but at the moment we really don't understand it." McConkey is just one of a growing number of people who is convinced that what is really needed now is a "chimp genome project" to help make sense of our own genome.

The human genome is not as special as we might imagine. The lowly nematode worm, for instance, shares as much as 75 per cent of its genome with us. To find out which genes make us uniquely human, say McConkey and others, we must compare our genome with that of our closest relative, the chimpanzee. There is just 1.5 per cent difference between our genome and the chimp's, and putting one alongside the other could help to answer some important questions, such as why humans get Aids but chimps do not, and what makes us act in our characteristically "human" way.

"The only way to understand the human genome fully is to take a comparative approach," says Walter Messier, a researcher at Genoplex, a Colorado-based biotech company that has begun comparing human genes with their chimp counterparts.

Already the company has identified two potentially important genes - one that they think is responsible for protecting chimps against Aids, and another that may play a role in learning and memory. Until their patents are approved they are keeping quiet about details. Messier thinks it unlikely that a publicly funded chimp genome project will ever come about, "but I think it will be sequenced by a private company", he says. "If a company had a chimp genome, people would be knocking at its door."

Others are more hopeful that public funding can be found. Last month, a group of scientists including McConkey sent a formal proposal to the Human Genome Organisation (Hugo). They asked for funds to set up a "Human Genome Evolution Project", which would include sequencing the chimp genome, as well as one of our other primate cousins. When the Human Genome Project ends, there will be hundreds of expensive sequencing machines sitting silently in labs around the world. "After the human genome is finished, everyone agrees that the mouse should be next, but what then?" says Ajit Varki, a biochemist at the University of California, San Diego. Mice are important because they are routinely used to establish the function of human genes, but Varki and others believe that the chimp should be next.

Luckily, the chimp genome's closeness to our own could make sequencing quick and, therefore, relatively cheap. The first documented genetic difference between humans and great apes was found only a couple of years ago by Varki. He noticed that human cells lack sialic acid, a sugar, on their surface, setting us apart from every mammal so far studied, including chimps and gorillas. Varki was able to trace the difference back and found that we are missing a critical segment of a 500 million-year-old gene. "This sugar is expressed at high levels throughout the bodies of all mammals, except in the brain. But in humans, we've got rid of it completely," Varki says.

Human cancer cells contain sialic acid, and our unique cell surface could explain why we are susceptible to infectious diseases such as malaria and cholera.

If and when a chimp genome project is completed, it is likely to find that just a handful of genes distinguish us as humans. With about 100,000 human genes, and given the 1.5 per cent variation between human and chimp DNA, it might be expected that about 1,500 genes separate our two species. "Most of those sequence differences will not be interesting, but a few will be crucial," Messier says. Latest estimates from the Human Genome Project suggest that there could be as few as 40,000, human genes, driving down the number of unique genes.

Just how a small number of genes could be responsible for the differences between humans and chimps is a question that any chimp genome project would need to address. Messier believes that we tend to overstate the differences. But, he adds, a single gene can also have a major impact. One that allows brain cells in a developing foetus to go through one more round of cell division, for example, could explain why our brains are twice the size of chimps'. And the so-called regulatory sequences, which control when and where genes are expressed, can subtly alter development.

Like its human counterpart, a chimp genome project would not be without problems and could even raise the spectre of genetically engineered chimps. "We cannot expect to produce mice that dance the tango, play chess or solve differential equations," says McConkey. That is why his proposal to Hugo includes a specific recommendation that the creation of transgenic chimps be ruled out.

While a chimp genome project would probably not be of much interest to chimps, if it does come about, it could well be in their best interests.

US Human Genome project: www.ornl.gov/hgmis/.

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