BOSTON--The annual meeting of the American Association for the Advancement of Science (publisher of Science), held from 15 to 19 February, included symposia across the scientific disciplines. According to one presentation, the number of human genes may actually be much closer to the early prediction of 70,000 genes rather than the much smaller number predicted when the draft sequence was published last year. ...So even with the human genome sequenced, we still don't know how many genes we have. And yet we are sure that humans evolved from lower organisms! Perhaps more humility would be appropriate. Furthermore, if the genomes of humans and other eukaryotes are so much different than those of prokaryotes, this could also pose a problem for the theory of evolution, namely, how these more complex genetic mechanisms evolved. In addition, there could be even more than 70,000 genes, because some genes may be only rarely expressed, and would not be detected by the SAGE technique.
When the draft human genome sequence was completed last year, a computer analysis suggested that the number of genes was shockingly small. Now, an experimental approach suggests that the number may actually be much closer to the early prediction of 70,000 genes, according to a presentation on 16 February.
Later in the day, Victor Velculescu mounted a small rebellion by raising the gene count. He and his colleagues, at Johns Hopkins University in Baltimore, Maryland, have gone back to the lab to look for genes that the computer programs may have missed. Their technique, called serial analysis of gene expression (SAGE), works by tracking RNA molecules back to their DNA sources. After isolating RNA from various human tissues, the researchers copy it into DNA, from which they cut out a kind of genetic bar code of 10 to 20 base pairs. The vast majority of these tags are unique to a single gene. The tags can then be compared to the human genome to find out if they match up with genes discovered by the computer algorithms. Velculescu said that only roughly half of the tags match the genes identified earlier--evidence, he says, that the human inventory of genes had been underestimated by about half.
The reason for the disparity may be that the standard computer programs were largely developed for the genomes of simple (prokaryotic) organisms, not for the more complex sequences found in the genomes of humans and other eukaryotes. "We're still not very good at predicting genes in eukaryotes," said Claire Fraser of The Institute for Genomic Research in Rockville, Maryland. It's entirely possible that there could be more than 32,000 genes, and SAGE is an important approach to finding them, she says: "You absolutely have to go back into the lab and get away from the computer terminal."
(AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE ANNUAL MEETING: Human Gene Count on the Rise Ben Shouse Science Feb 22 2002: 1457.)
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