Gao, 60K human genes?
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Scientists bet on how many genes will fit in the human genome
Friday, July 21, 2000
By JOHN MANGELS PLAIN DEALER SCIENCE WRITER
How many genes do we humans carry inside us, lurking in the tangled whorls of our DNA?
It's a question scientists have batted around for years, but haven't had the tools to tackle until recently. Millions of dollars in potential research profits, not to mention a rowdy bar bet this spring among an international group of geneticists, are riding on the outcome.
And the answer is ... about 60,000 - if you believe Celera Genomics, the brash Rockville, Md. biotech company. Not everyone does.
The estimate is as specific as Celera is willing to get, for the moment. The controversial firm, which has led a monumental effort to catalog the billions of bits of human genetic material, hasn't officially announced its finding, but disclosed the 60,000 figure during a meeting with Cleveland researchers earlier this week.
"We believe that's the total," said Daniel Clutter, a biochemist who serves as Celera's regional account manager. "We're pretty sure it's less than 60,000 genes. We may find a few more that were not predicted" by the computers doing the analysis.
Celera has been discussing the finding internally for a couple of weeks, Clutter said, but was reluctant to say more publicly until the results can be reviewed and published in a scientific journal. Such journals have strict rules against disclosure of information until it is published in their pages. Celera's own Web site still uses an estimate of 100,000 human genes.
Genes are the bits of inherited material that control the assembly and functioning of living organisms, from simple yeast to people. Although scientists have identified individual human genes and figured out what some of them do, until now no one has been certain how many we have. Estimates have ranged from the mid-20,000s to 140,000 or more. A group of geneticists gathered for a conference at Cold Spring Harbor, N.Y., in May set up a betting pool while relaxing in a pub after hours, with the lowest of the 228 guesses to date at 27,462 genes, and the highest at 200,000.
By comparison, the tiny, dirt-dwelling roundworm Caenorhabditis elegans has about 19,000 genes; the common fruit fly Drosophila melanogaster 13,600.
The number is important, monetarily and medically. The more genes an organism has, the more difficult it may be for scientists to determine how those genes work together to keep the body functioning properly or to cause disease. But lots of genes also could mean lots of green, if commercial genetics companies can decipher what a specific gene does and file a patent or otherwise find a way to profit from its discovery.
Celera and a government/academic team have been in a race to decode the chemical makeup of the genetic material found in almost every human cell - the long, twisting strand of DNA that is a mix of genes and seemingly inactive "junk." The first part of the competition ended in a tie in June when the bitter rivals jointly declared they were done.
The next task is to figure out which parts of DNA are genes and which are not. Both Celera and the government/academic group (known as the Human Genome Project) are using powerful computer programs that prowl through the DNA sequence, looking for familiar strings of chemical "letters" that match components of known genes. It's like scanning faces in a crowd, trying to identify relatives you haven't met before, based on how you and your immediate family look.
So far, the methodical Human Genome Project has identified about 38,000 human genes but is still looking. Celera, which has ultra-fast computers and whose motto is "Speed Matters," says the final total is 60,000, give or take.
Others are skeptical, though. Huntington Willard, an internationally known genetics researcher who heads Case Western Reserve University's Center for Human Genetics and directs University Hospitals' Research Institute, doesn't doubt Celera has identified 60,000 genes. But he isn't convinced that is the final tally.
Since the search computers depend on recognizing familiar gene fragments, "you by definition can't find anything truly new," Willard said. The machines would likely miss unconventional-looking genes.
Also, individual genes have multiple forms, depending on what task they're doing. Rather than counting genes themselves, a leading California biotech company called Incyte Genomics thinks it's more important to look farther down the genetic production line, identifying evidence of the various types of work a gene is doing. Such indicators are called gene transcripts, and Incyte estimates there are 140,000 or more in humans.
"The easy impression one can get [from Celera's revelation] is that the game is over," said Incyte chief executive officer Roy Whitfield. "But it's far from done."
The betting pool won't attempt to declare a winner until 2003, by which time organizer Ewan Birney hopes things will have become clearer. The $1-per-wager pool has a strict definition of what constitutes a gene, and Birney, a scientist at England's European Bioinformatics Institute, doesn't want to weigh in on the likelihood of Celera's estimate being right. "This is full of gene politics," he said.
e-mail: jmangels@plaind.com Phone: (216) 999-4842
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