BETHESDA, Md. _ Scientists in the U.S. and Europe saidWednesday they have achieved "a major milestone" in genetics bysuccessfully sequencing all of the 12,057,500 base pairs that make upthe yeast genome.

The effort, carried out by 92 laboratories around the world, produceda detailed map of the largest and most advanced genome sequencedso far _ and the first from an organism whose structure resemblesthat of human cells.

Francis Collins, director of the National Center for Human GenomeResearch here, said, "The yeast genome is closer to the humangenome than anything completely sequenced so far. It will allow us tomove into a whole new area of biology _ looking at how all thegenetic instructions work together to make a whole cell function."

Philip Heter, of the Johns Hopkins University School of Medicine, inBaltimore, said, "The completion of the yeast gene sequencerepresents an enormous achievement that will not only benefit yeastgenetic research, but also will accelerate the pace with which crossreferences can be made to genes involved in human disease."

The sequences of the 6,000 genes in yeast, Saccharomycescerevisiae, now are available in laboratory data bases in the U.S. andEurope. They soon will be available in this country throughGenBank, the data repository of the National Center forBiotechnology Information, and in Europe through the EuropeanMolecular Biology Laboratory data library.

Scientists said the achievement announced today in press conferencesin the U.S. and Brussels represents a watershed in molecular biology,one that will lead to an even more detailed understanding of cellfunction at a basic level in organisms of increasing complexity.

To date, several viral genomes have been sequenced, and less thanone year ago, Craig Venter, of the Institute for Genomic Research, inGaithersburg, Md., and Hamilton Smith, of Johns HopkinsUniversity, in Baltimore, announced they had spelled out thecomplete sequences of two species of bacteria: Haemophilusinfluenzae and Mycoplasma genitalium.

But bacterial cells are far simpler than yeast cells. And yeast cellshave a nucleus and compartmentalized anatomy for carrying outspecific cell functions much like human and other mammalian cells.

"Our understanding of human biology is going to be greatlyfacilitated by this work," Collins said.

Ron Davis, of the genome research program at Stanford University,in Palo Alto, Calif., said the yeast genome has 16 chromosomes.Because it divides much as human cells do, the genetic controlmechanisms involved in yeast cell division are believed to be muchthe same as those in humans.

Study of these mechanisms should greatly enhance medicine'sunderstanding of cancer, Davis said.

Knowing all of the genes in yeast should also speed the pace andefficiency of gene research.

Before the 6,000 yeast genes were sequenced, Davis said, scientistswere forced to study the organism as if it was a "black box _ wecould fish out some genes but we would never know if we had all ofthem."

Now researchers will know what genes are there and what genes arenot, so they can design more focused experiments. The knowledgewill also significantly cut the cost of genetic research, Davis said.

In the past, he said, "we had to look at genes one at a time." Nowresearchers can scan the entire genome for sequences that matchthose from other organisms, including humans, that play an importantrole in normal cell function _ and in cellular malfunctions.

One In Four Disease Genes Matched A Yeast Gene

Heter, of Johns Hopkins, said the researchers, curious to know howoften yeast genes matched those found in human disease, decided tofind out by comparing 52 known human disease genes found usingpositional cloning with the 60 percent of the yeast genome that hadbeen sequenced at the time of the experiment.

"We found that one of four of the human disease genes _ or 25percent _ matched a yeast gene with very high stringency, suggestingthat cross-referencing will be very productive," Heter said.

Ten years ago, he said, the gene that causes cystic fibrosis was foundto code for a protein that was similar to one produced by a gene inyeast. The two genes were not functionally identical but belonged tothe same family, which permitted scientists to use yeast as alaboratory model to study the function of the cystic fibrosis gene.

Less than a year ago, the gene for ataxia telangiectasia was clonedand found to be similar to a yeast gene that is involved in cell-cycleregulation. This is particularly significant because the ataxiatelangiectasia gene renders many people susceptible to cancer. "Nowthe biology of this yeast protein can be applied to understanding themechanism of this predisposition to cancer," Heter said.

The effort to sequence the yeast genome began in 1989, led by AndreGoffeau, of Belgium, who organized a collaboration among severallabs in Europe. The project expanded to include labs in the U.S.,Canada, U.K. and Japan, among many others.

In the U.S., the laboratories at Stanford University and WashingtonUniversity sequenced about one-fifth of the yeast genome. Goffeaucoordinated the project from the Catholic University of Louvain inBelgium.

"In 1993, we made a `gentleman's agreement' not to compete,"Goffeau said in a statement released by the National Center forGenome Research. "We agreed not to stake out any territory, and onseveral occasions, DNA fragments to be sequenced wereredistributed according to the respective abilities of the sequencingteams."

The biggest challenge lies ahead _ figuring out what each gene does.So far, the researchers said, they have determined the function ofsome 3,000 yeast genes. n

-- Steve Sternberg Special To BioWorld Today

(c) 1997 American Health Consultants. All rights reserved.