Secret code of Man may be surprisingly short

The total number of human genes - a mystery that the world's best biologists have yet to solve - is estimated in aseries of new studies to be much lower than was thought possible.

The total number of human genes - a mystery that the world's best biologists have yet to solve - is estimated in aseries of new studies to be much lower than was thought possible.

Most scientists believed there must be between 70,000 and 100,000 genes responsible for providing the digital recipe for making a human being, with some estimates running as high as 140,000. But now two independent teams of researchers are to publish what may be the best estimates yet - and both come to the conclusion that it takes fewer than 35,000.

The findings, in the June issue of the journal Nature Genetics, are being treated seriously because the two groups have used separate methods to calculate the gene number and both have had access to the actual data on DNA from the international human genome project. If the estimates prove accurate it will mean that many scientists will lose money on bets they have placed on the total number of human genes. Nearly all believed it would turn out to be significantly greater than 40,000.

However, they have seriously overestimated the genetic complexity of humans, according to Brent Ewing and Philip Green, of Washington University in Seattle, and Jean Weissenbach and colleagues at the French national gene sequencing centre, Genoscope, in Evry. Ewing and Green estimate that there are just 34,000 human genes, based on an analysis of the known DNA sequence of chromosome 22, one of the few human chromosomes to be fully deciphered.

Weissenbach comes to an even lower estimate of just 30,000 genes based on a neat method of comparing the human DNA sequence with that of other animals, notably the genome of the puffer fish.

The findings also match the startling revelation that human chromosome 21 - which has just been fully decoded - contains so few genes that some scientists have dubbed it a "genetic desert".

Samuel Aparicio, a gene scientist at the Wellcome Trust centre for molecuar mechanisms in disease, Cambridge, said the higher estimates were based on counting the "messenger molecules" that acted as intermediates between genes and the proteins they code for. "The central lesson is that it's a mistake to take the numbers of intermediates and say they must correspond to the single genes," Dr Aparicio said.

In a separate analysis of the gene-counts, also published in Nature Genetics, Dr Aparicio warns there is a possibility that the two groups may have underestimated the number. "However, it seems unlikely that these estimates will prove wildly inaccurate," he said.

Flies and worms have about 15,000 genes and it is thought that the human genome has gone through a dramatic gene doubling at least twice in evolutionary history, bringing the total to no more than 60,000 genes, Dr Aparicio said. "This puts an upper limit on the total number of genes. If you then take into account that genes are lost over time, you go back to a number not far off what is being suggested," he said.

Higher estimates of more than 100,000 genes have usually come from biotechnology companies involved in gene sequencing. Some scientists now believe that these inflationary estimates may have something to do with making the DNA databases of these companies appear more attractive to potential investors.

In an editorial, Nature Genetics warns that the brouhaha over the number of human genes should not eclipse the higher goal of the genome project. "Even with a completely annotated genome to hand, we will still face the task of fathoming how it works," the journal says.

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