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Yeast Genome Revised
By Nancy Touchette

Ever since the yeast genome was sequenced seven years ago, researchers have debated the best way to identify the “true” genes—those DNA sequences that code for proteins. Now, researchers have sequenced three more yeast genomes and say that the current list of genes needs to be revised.

The importance of the common baker's yeast, Saccharomyces cerevisiae, to biologists is revealed in this T-shirt logo.

By comparing the new genome sequences with the original, the researchers uncovered nearly 50 new genes and 70 stretches of DNA that regulate yeast genes. They also propose that about 500 DNA sequences previously thought to be genes should be crossed off the list.

The research, published in Nature, goes far beyond bread and beer: It could serve as a model for identifying every gene in the human genome. Furthermore, many yeast genes have counterparts in humans, including some that play a role in cancer.

“This study shows how valuable it is to sequence the genomes of closely related species,” says Steven L. Salzberg of the Institute for Genomic Research (TIGR) in Rockville, Maryland, who wrote an accompanying News & Views article. “If we line up the genomes and see the same sequences in each species, it tells us that a gene is important.”

“This is just what we need to do, and in fact are doing, with the human genome,” he adds.

When the budding yeast, Saccharomyces cerevisiae—used to make beer and bread—was sequenced in 1996, researchers found nearly 6,000 likely genes (based on the length of the sequence and the presence of specific signals that indicate where genes begin and end). Subsequent estimates have ranged from 4,800 to 6,400 genes. According to the Nature paper, the number should be 5,538 genes.

In the new study, Manolis Kellis, a graduate student in Eric S. Lander’s laboratory at the Whitehead Institute in Cambridge, Massachusetts, and his colleagues analyzed the three other yeast species and compared them to S. cerevisiae.

Scanning electron micrograph of S. cerevisiae.

“For each possible gene sequence, we looked to see if there was evolutionary pressure to preserve that stretch of DNA,” says Kellis. “We discarded about 500 sequences that were not conserved. Evolution had no reason to care about these sequences.”

For Kellis, the study’s most exciting discovery was finding more than 70 new sequences that regulate gene activity.

“We found two types of regulatory sequences,” he says. “Some sequences act like little tiny traffic lights, telling the gene when to turn on and when to turn off. Others act as zip codes, or shipping addresses. They tell the cell where to send the message, once a gene is made into RNA.”

The researchers also found that the most variation in yeast genes occurs on the ends of chromosomes, in regions known as telomeres. Telomeres have not been completely sequenced in the human genome.

“Telomeres get exchanged a lot more rapidly,” says Salzberg. “My twenty-five cent bet is that the same thing is going on in humans. I would like to see telomeres sequenced in humans. This is where things are most likely to be happening, where gene rearrangements are likely to occur.”

He adds, “We need to finish the human sequence down to the last base.”

. . .

M. Kellis et al. Sequencing and comparison of yeast species to identify genes and regulatory elements. Nature 423, 241-254 (May 15, 2003).
S. Salzberg. Yeast rises again. Nature 423, 233-234 (May 15, 2003).

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