On 12 February, during an historic event that was broadcast around the world, journalists gathered for a press conference organized by Science magazine to present the results of the near-final sequencing of the human genome. The news event was led by J. Craig Venter of Celera Genomics and Francis Collins, leader of the publicly-funded International Human Genome Sequencing Consortium. Both groups will publish their results this week -- Celera in Science and the Consortium in Nature -- and both will provide researchers with free access to their findings.

THE SCIENCE PAPER

The human genome sequence published in the journal, Science estimated to have an average sequencing accuracy of 99.96 percent and color-coded to propose functions for two-thirds of all identified genes reveals an ancient script that's strikingly common across all ethnic groups, and only about twice as large as a fruit fly's genetic blueprint.

Accurately covering 95 percent of the genome, the sequence sets the total number of human genes somewhere between 26,383 and 39,114. If the final tally lies somewhere in between, say, around 30,000, then people have only about 13,000 more genes than the fruit fly, Drosophila melanogaster, according to the Science paper, by lead author J. Craig Venter of Celera Genomics and 282 others.

This range is surprisingly low: Some researchers had predicted up to 140,000 genes in the human genome.

"This stunning accomplishment, representing the most accurate human genome sequence ever completed, offers new and exciting prospects for targeting new medical improvements," said Science Editor-in-Chief Donald Kennedy. "It can tell us much about our place in the diverse panorama of life." Also revealed by the Science paper are vast stretches of desert-like regions, where the human genome sequence contains relatively few or no protein-coding genes. About one-fourth of the genome could be considered deserts, with lengthy gene-free segments. Gene density is greatest along chromosomes 17, 19 and 22, but chromosomes X, 4, 18, 13 and Y are comparatively barren. "Genes exist largely in islands or clusters separated by large deserts millions of base pairs in length that have few or no genes," the paper concludes.

More than a third of the genome (35.3 percent) contains repetitive sequences, suggesting that this so-called "junk DNA" deserves further study. In fact, chromosome 19 is 57 percent repetitive. In addition to repeated segments, the Science paper identifies 2.1 million genetic sequence oddities or variations. Known as SNPs, or single nucleotide polymorphisms, these differences between people are usually harmless, the Celera team reported, since less than 1 percent result in potentially dysfunctional proteins. Preliminary evidence suggests that these differences are not random events because they are distributed unevenly across chromosomes.

Every person on Earth shares 99.99 percent of the same genetic code with all other people. In fact, people from different racial groups can be more genetically similar than individuals within the same group. Individual variations represent about 0.10 percent, or 1 in 1,250 different "letters" in the entire sequence, the Science paper confirms.

These genetic instructions are all contained within 46 large DNA-containing molecules called chromosomes 23 from each parent. Inside chromosomes, sugar-phosphate chains are linked by pairs of the chemical bases: A, C, G and T (adenine, cytosine, guanine and thymine). Together, these letters form the "steps" within DNA's ladder-like structure. They also carry the code for synthesizing new proteins and creating life.

IMPLICATIONS

The completed human genome sequence is expected to promote medical advances such as diagnostic tests, pharmaceuticals that reflect individual genetic variations, and perhaps gene therapies targeting segments of code responsible for disease. SNPs will help scientists identify the basis of many genetic diseases, and therefore provide targets for new treatments. They also may help us resolve academic questions about our common ancestry, as well as the movement of people and cultures around the world.

"The challenge now will be to stop thinking about one gene at a time and start trying to understand the whole set at once as a complex system to think about how such a small number of genes can generate a fly or a person," commented Barbara Jasny, a supervisory senior editor at Science who handled the Celera manuscript. "Ongoing research should further investigate the functions of repetitive DNA, the regulation of gene expression, protein interactions, signaling, effects of the environment and other mechanisms that may contribute to an organism's complexity."

Indeed, "There are no 'good' genes or 'bad' genes, there are merely networks that exist at various levels and at various connectivities, and at different states of sensitivity to perturbation," concluded Venter, Celera's president and chief scientific officer. "The notion that one gene equals one disease, or that one gene produces one key protein, is flying out the window."

The Science paper reveals, for example, that the genome includes "recombination hot spots," where the rate at which genetic elements occurring on paired chromosomes recombine with one another may be much higher than in other regions.

Venter's research group cautioned, however, that human health, behavior and characteristics are influenced by many factors. Genetic information must therefore be used wisely.

"This assembly of the human genome sequence is but a first, hesitant step on a long and exciting journey towards understanding the role of the genome in human biology," the Celera group concluded. "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 sequence 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 the future, they wrote, "The real challenge of human biology, beyond the task of finding out how genes orchestrate the construction and maintenance of the miraculous mechanism of our bodies, will lie ahead as we seek to explain how our minds have come to organize thoughts sufficiently well to investigate our own existence."