The short, simple human gene map
Humans are complex despite fewer genes than expected, most of them shared with other species.
ST. LOUIS — Scrambling to unlock the secrets of the human genetic code, researchers stand on the kind of scientific threshold that appears once every century or so. They're poised to understand the forces behind evolution, explode racial myths, change the way doctors diagnose disease, and try to help people live longer.
But the first mystery along this long road of scientific discovery boils down to this: If man is so advanced, how come his gene count doesn't look that much different from a weed's or a worm's?
The question is forcing scientists to reevaluate their notions of biological complexity and mankind's place in the natural order. "At a basic level, I can assure you we're a lot more complex than worms," says Robert Waterston, director of the genome sequencing center at Washington University here in St. Louis. "The question becomes: How do we account for that complexity?" In this week's issue of Nature, Dr. Waterston and his colleagues at the publicly funded Human Genome Sequencing Consortium reveal that humans possess roughly 32,000 genes. In a separate article to be published in this week's edition of the journal Science, researchers at the privately funded Celera Genomics Corporation also confirmed that the human genome contains between 26,000 and 39,000 genes. That's far fewer than what many scientists were predicting only last year when, in one of science's great rivalries, Celera and the consortium rushed to publish rough drafts of the entire human genome sequence.
That string of biological code proved so long - some 3 billion units - scientists had expected it to contain instructions to create anywhere from 50,000 to 140,000 genes. Instead, they have discovered that vast stretches of the code create very few genes.
So what makes us complex?
"It appears that the human genome does indeed contain deserts, or large, gene-poor regions," writes Craig Venter, president of Celera, and 282 other authors in the Science article. Furthermore, just over a third of the human genome contains repetitive sequences that scientists label "junk DNA" because, at the moment, they don't appear to have any function. Researchers will spend coming months taking a deeper look.
The lack of human genes poses a conundrum for scientists. If humankind only has 13,000 more genes than Caenorhabditis elegans (a roundworm) or 6,000 more than Arabidopsis thaliana (a weed), what makes people so advanced by comparison?
Geneticists have many possible theories. For example, complexity may stem from combinations of genes. Since 30,000 genes can combine in far more ways than 20,000, these combinations alone may be enough to explain human complexity. Also, there's evidence that genes in vertebrates work harder by producing more kinds of proteins than the genes in worms and flies.
Then there are parts of genes, known as domains, that get shuffled around into new architectures. Scientists are finding that humans have far more combinations of these architectures than simpler life forms. Finally, there are some genes that humans have that worms and flies don't have. Their presence may account for man's uniqueness.
But these are guesses. And if, as suspected, the chimpanzee genome turns out to be stunningly similar to the human genome, then scientists may still be stuck trying to explain how one species has come to so dominate the world in the past 50,000 to 150,000 years while others are still climbing or buzzing around trees.
Scientists have also found some 200 genes that humans share with bacteria but not with the higher-order worm or fruit fly. That suggests humans have acquired some genes through other mechanisms than direct inheritance, says Waterston. While scientists understand something about how bacteria can directly transfer genes, how humans acquired them remains a mystery, he adds.
"No doubt the genomic view of our place in nature will be both a source of humility and a blow to the idea of human uniqueness," Svante Paabo of Germany's Max Planck Institute of Evolutionary Anthropology writes in a separate article in Science. But, he continues, "the realization that one or a few genetic accidents made human history possible will provide us with a whole new set of philosophical challenges to think about."
Human genomic research could also explode popular perceptions about racial differences. For example, the new research suggests that all individuals are 99.99 percent alike. And researchers are finding that the gene pool in Africa, where man is thought to have originated, remains more diverse than in the rest of the world. These findings undermine sweeping notions of differences based on skin color, scientists say.
"It is often the case that two persons who descend from the same part of the world, and look superficially alike, are less related to each other than to persons from other parts of the world who may look very different," Dr. Paabo writes.
The darker side of genetics
But the new science could unwittingly usher in a new era of genetic discrimination. For example, if scientists create diagnostic tests that can determine an individual's predisposition to certain diseases, should that person's insurance company or employer know about it? Many states ban the practice, but no specific national laws exist. And the federal laws that might apply have not yet been tested in the courts.
"Without adequate safeguards, the genetic revolution could mean one step forward for science and two steps backwards for civil rights," write United States Sens. James Jeffords (R) and Tom Daschle (D) in a separate article in this week's Science. "Misuse of genetic information could create a new underclass: the genetically less fortunate."
On Friday, for the first time ever, the federal Equal Employment Opportunity Commission sued an employer - Burlington Northern Santa Fe Railway - for discrimination based on genetic testing.
In a survey of 2,133 employers last year by the American Management Association, seven said they are currently using genetic testing for job applicants or employees, according to Science.
It's not yet clear whether having fewer genes to study - 30,000 instead of, say, 100,000 - will speed up anticipated medical advances. That's because the new science already gives researchers ways to study thousands of genes at a time. The key will be how easily scientists can turn their enhanced understanding into practical applications.
What is clear is that the new approach - looking at systems of genes rather than individual genes - will transform biologists' view of the human body. "Before we were looking through a keyhole," says James Pierce, a professor of genetics at the University of the Sciences in Philadelphia. "Now, the door is open."
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