Why you can't judge a man by his genes 

Mark Henderson / London Times 12feb01

THE two completed maps of the human genetic code reveal a treasure trove of information about the essence of mankind. They include the discovery that human beings have many fewer genes than expected.

Scientists now know that the human genome probably contains only 30,000 genes, the vast majority of which are shared with other animals, and as a result are revising ideas about human development and behaviour.

The number of genes — barely twice as many as the fruit fly and only 4,000 more than a garden weed called thale cress — is simply too small to support the idea that human beings are “hard-wired” by the DNA they inherit from their parents. Instead, researchers now believe that the complex ways in which genes operate in the body, and the environmental factors that influence every individual in unique fashion, may be more important than raw genetic material. The debate about the balance between nature and nurture is back on the agenda.

While scientists from the rival public and private-sector genome projects are at odds over which version is more definitive and more useful to future research, they are largely agreed about the low number of genes, and about the significance of this discovery. The American company Celera sets the total number as not less than 26,383, and not more than 39,114, while the public-sector project has arrived at a range of 30,000 to 40,000. Both think that the final number will be in the low 30,000s, a figure many times lower than past estimates, which have ranged as high as 150,000.

Attention is now turning to the much larger numbers of proteins that those genes allow human beings to produce — there are more than 250,000 — and to the way in which the functions of genes are affected by the environment.

Craig Venter, president of Celera, said that the findings proved that while genes were vital to human development, they could not be the only, or even the major, factor in the behaviour or many diseases. “There are two fallacies to be avoided: determinism, the idea that all characteristics of a person are hard-wired by the genome; and reductionism, that now the human genome is completely known it is just a matter of time before our understanding of gene functions and interactions will provide a complete causal description of human variability.

“In everyday language the talk is about a gene for this and a gene for that. We are now finding that that is rarely so. The number of genes that work in that way can almost be counted on your fingers, because we are just not hard-wired in that way.”

The true benefit of genome research for medicine was likely to be greater understanding of the way in which genetic variability made some people more or less susceptible to certain environmental influences, Dr Venter said. He cited the example of a genetic variation implicated in colon cancer, which is expressed throughout the bodies of those who have it. Only in the colon, however, is it exposed to the environmental toxins that damage its ability to work properly, causing tumours to form.

“You cannot define the function of genes without defining the influence of the environment. The notion that one gene equals one disease, or that one gene produces one key protein, is flying out of the window.”

Sir John Sulston, former director of the Sanger Centre, near Cambridge, which sequenced a third of the genome for the public project, said that the key to the complexity of human beings was the way in which human genes had many different functions.

“We know that as we move up the ladder of complexity from the single-cell creatures, through small animals like worms and flies, and up to us, what we are adding on is control genes,” he said. “We are not adding so many genes performing new functions, what we are doing is to increase the variety and subtlety of genes that control other genes.”

Both research teams, who publish their findings today in the journals Nature and Science, have uncovered large numbers of tiny genetic variations between individuals, called “single nucleotide polymorphisms”, or “snips”. Celera has found 2.1 million snips, and the public team 1.4 million, and many millions more are yet to be located. Only a few thousand of them, however, will govern significant biological events that might have a potential use in medicine, Dr Venter said.

“Between 1,000 and 10,000 of the snips probably result in the biological differences between any two of us. Those are the ones that we think are biologically significant.” Other snips, he said, would be valuable only as “mapping tools”, and could also be used for “personal identification and forensic purposes”.

source: http://www.thetimes.co.uk/article/0,,2-82213,00.html 13feb01