Comprehensive look at genetic code shows humans have remarkably few genes

In a pair of landmark studies that offer the first detailed look at virtually the entire human genetic code, scientists say they see remarkably few genes - not all that many more than in a fruit fly.

In a pair of landmark studies that offer the first detailed look at virtually the entire human genetic code, scientists say they see remarkably few genes - not all that many more than in a fruit fly.

The research also revealed new leads for finding roots of disease and confirmed that men can take the blame - or credit - for creating most inherited genetic mutations.

The analyses were performed by the two teams that made headlines last year for determining nearly all the "letters" of the human DNA code. That 3-billion-letter code, called the genome, is a chemical sequence that contains the basic information for building and running a human body.

"We suddenly have the global view, the view of the Earth from the Moon, and it's pretty thrilling," commented Dr. Harold Varmus, a former director of the National Institutes of Health who now heads the Memorial Sloan-Kettering Cancer Center in New York.

The genome work is expected to help scientists find disease-promoting genes, develop better drugs, tailor therapies to particular patients, evaluate environmental hazards and study human evolution and migration.

One scientific team, a consortium of federal and institutional researchers in the United States and scientists in five other countries, is publishing its results in Thursday's issue of Nature. The other team, centered at Celera Genomics in Rockville, Maryland, is publishing in Friday's issue of Science.

The two teams, which worked independently, estimated roughly the same number of human genes: about 26,000 to 39,000 according to Celera, and about 30,000 to 40,000 according to the consortium. Scientists with both groups said the best bet is something fewer than 35,000.

That's surprisingly low, leaders of both scientific teams said.

While the result agrees with some recent estimates, it's in the lower range of what scientists have thought. Some researchers put the count above 100,000 genes.

The new estimates are fairly close to the 25,000 genes in the small flowering plant called Arabidopsis thaliana, the 19,000 genes in the tiny worm C. elegans, or the 13,600 genes in the fruitfly Drosophila.

"There are many people who are bothered by the fact that they don't seem to have (many) more than twice as many genes as a fruit fly," said Eric Lander, director of the Whitehead Institute Center for Genome Research in Cambridge, Massachusetts, and a member of the international consortium.

"It seems to be some kind of affront to human dignity."

So why are humans so much more complex than a fruit fly or worm?

That remains a mystery. But scientists stress that the sheer number of genes is only a starting point for creating complexity.

Most genes exert their effects by telling the body make certain proteins, and human genes are more likely than fly or worm genes to give rise to multiple proteins rather than just one. What's more, human proteins are more versatile, scientists say.

And the timing of when genes turn on and off, and in what tissues they are active, can also make a big difference in their effect.

Both groups also say their data have already helped scientists find genes that promote disease. The consortium's paper lists about 30 such genes found with the help of its data, and J. Craig Venter, president of Celera, said his group's database has led to finding of such genes as well.

Venter recalled that he had spent 10 years trying to find a particular gene, a task "that now can be done with a 15-second computer search." So scientists can quickly focus on studying a new gene rather than having to spend lots of time tracking it down, he said.

The consortium also confirmed a recent finding that men's bodies create inheritable mutations at about twice the rate of women's. Prior estimates had suggested the disparity was even greater.

The gender difference is a mixed message for men: It suggests they provide the greater force for evolutionary change, but also that they create more glitches that may promote disease.