By Sean Henahan, Access Excellence

BETHESDA, MD., (4/24/96- A worldwide collaboration of more than 100 laboratories has accomplished a significant first in scientific research, the sequencing of the complete genome of a complex organism, Saccharomyces cerevisiae, otherwise known as baker's yeast.

The achievement marks the complete sequencing of the largest genome to date - more than 12 million base pairs of DNA. I also represents the first sequencing of an organism whose cells are like those of humans.

"Now we know for the first time all the genes it takes to make a simple eukaryotic cell," says H. Mark Johnston, Ph.D., associate professor of genetics, Washington University, St. Louis.

"Yeast is a superb model for understanding the basic functions of human cells, which have to do nearly everything yeast cells do," Johnston adds. "As the human genome is sequenced, we will be able to compare human genes with those of yeast. When a similar gene is located, its function in humans can be deduced through experiments with yeast, which is much more amenable to genetic manipulation."

This strategy already has uncovered the functions of several human disease genes. For example, experiments with yeast revealed that a recently discovered gene that raises the risk for one type of colon cancer normally is involved in repairing damage to DNA.

Efforts to understand the genome of yeast began in the 1950s when Robert K. Mortimer, Ph.D., at the University of California, Berkeley began to genetically map all of the genes on the organism's 16 chromosomes. The second phase began in the early 1980s, when Maynard V. Olson, Ph.D., then at Washington University School of Medicine, created a physical map of the yeast genome by cloning overlapping DNA fragments. This map provided the starting point for the final phase, which has determined the order of the approximately 12 million nucleotide building blocks in the yeast genome.

The sequencing of the yeast genome began in 1989 under the direction of Andre Goffeau, Ph.D., a biochemist at the Catholic University of Louvain-La-Neuve in Belgium who coordinated a network of more than 70 laboratories in the European Union. The Europeans sequenced 55 percent of the genome, 17 percent was sequenced at the Sanger Centre in England, 15 percent at Washington University, 7 percent at Stanford University, 4 percent at McGill University in Canada and 2 percent at The Institute of Physical and Chemical Research (RIKEN) in Japan.

"This is a major milestone in the Human Genome Project. The spirit of cooperation among laboratories throughout the world sped the completion by as much as two years," said Robert H. Waterston, M.D., Ph.D., who directed the work at Washington University.

The group sequenced all of chromosome VIII and parts of chromosomes IV, XII and XVI. Johnston annotated the sequences and made them freely available in GenBank, a repository maintained by the National Center for Biotechnology Information in Bethesda, Md.

The yeast chromosomes were sequenced from tip to tip with no gaps, and both strands of the double helix of DNA were analyzed, resulting in an accuracy rate of more than 99.99 percent. Because of the composition of the yeast genome, it is unlikely that any other genome sequence ever will match that standard, researchers note.

The biggest surprise was that more than half of the 6,000 genes uncovered during the sequencing were unknown, despite decades of intense scrutiny by yeast geneticists. Preliminary studies suggest that a large proportion of yeast genes code for nuclear proteins, such as transcription factors that turn other genes on and off. Genes for membrane proteins that ferry substances in and out of the cell also are well represented.

The next challenge will be to figure out the precise functions of all of the genes in the yeast genome. The European Union has launched a systematic effort by giving each lab a set of genes to mutate. The researchers will look at the effect of each missing gene on the organism's day to day activities.

The yeast genome has a lot of similarities with the human genes. Discovering the precise function of each of these genes, which will be the next task for scientists, should help us understand the origin and the evolution of more than forty diseases, including colon, breast and ovarian cancers, adrenoleukodystrophy, cystic fibrosis, ataxia telangiectasia, amyotrophic lateral sclerosis, achondroplasia and Duchenne muscular dystrophy. Moreover, since yeast is very largely used in food industry, important repercussions can be expected in this area as well.

The new findings were announced on 4/24/96 at two press conferences in Brussels, Belgium and at the National Institutes of Health in Bethesda, Md.

Related information on the Internet

MIPS Yeast Genome Project

Yeast Artificial Chromosomes

Human Genome Project