International Team Completes DNA Sequence of Yeast

International Team Completes DNA Sequence of Yeast

April 24, 1996

An international consortium of scientists announced today it has finished spelling out the entire genetic code of a species of yeast valuable to biologists and commonly used by bakers and brewers. The achievement required determining the order of all 12,057,500 chemical subunits contained in the yeast's nuclear DNA. Yeast contains the largest genome -- or full set of genetic instructions -- to be completely deciphered so far. Furthermore, the single-celled yeast is the most advanced organism yet to be sequenced, belonging, with humans, to a group called "eukaryotes." All eukaryotes share similarities in their cellular anatomy, including a distinct nucleus and compartmental structures for carrying out specialized processes.

Having the entire yeast DNA sequence now paves the way for scientists to study all the information encoded in the organism's genetic blueprint. Containing some 6,000 genes arranged on 16 chromosomes, yeast has already provided biologists with a valuable resource for determining the function of individual human genes involved in medical problems, such as cancer, neurological disorders, and skeletal disorders. Over the next few years, scientists in the United States and Europe will piece together for the first time a comprehensive look at how all the genes in a eukaryotic cell function as an integrated system.

"The yeast genome is closer to the human genome than anything completely sequenced so far," said Dr. Francis Collins, director of the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health (NIH). "The complete sequence will allow us to move into a whole new area of biology -- looking at how all the genetic instructions work together to make a whole cell function."

The yeast sequence information is available today in laboratory databases in Europe and the United States and will soon be deposited in the public database GenBank in the United States and the European Molecular Biology Laboratory data library in Europe.

The yeast sequencing initiative involved 92 laboratories the European Union, as well as labs in the United States, Canada, the United Kingdom and Japan. "In 1993, we made a gentleman's' agreement not to compete, but to divide the work among us in order to complete the sequence rapidly with as little duplication as possible," said Dr. Andre Goffeau, who coordinated the European Union initiative from the Catholic University of Louvain in Belgium. "We agreed not to stake out any territory and, on several occassions, DNA fragments to be sequenced were redistributed according to the respective abilities of the sequencing teams."

U.S. laboratories at Stanford University, led by Dr. Ron Davis, and at Washington University in St. Louis, led by Dr. Mark Johnston, collectively sequenced about 21 percent of the yeast genome as part of the U.S. Human Genome Project's mission to improve the efficiency of DNA-sequencing technologies. The U.S. work was supported by NHGRI's human genome program.

"The full yeast sequence will provide investigators supported by all the NIH Institutes with important new tools for studying virtually all aspects of normal and abnormal cells," said Dr. Harold Varmus, director of NIH.

The drive to sequence the yeast genome began in 1989 when Dr. Goffeau organized a group of European laboratories to take on the task. In 1992, the initiative scored a first when the scientists reported the complete sequence of one (chromosome III) of the yeast's 16 chromosomes. It was the first time a eukaryotic chromosome had been completely sequenced. As part of the Human Genome Project (HGP), U.S. and British sequencing laboratories later brought in large-scale automation to the yeast initiative, helping to finish the project some two years sooner than the scientists themselves had predicted.

Biologists have studied yeast, known by its scientific name Saccharomyces cerevisiae, for many decades because it offers valuable clues to understanding the workings of more-advanced organisms. Humans and yeast, for example, share a number of similarities in their genetic make up. For one, many regions of yeast DNA contain stretches of DNA subunits, called bases, that are very close or identical to those in human DNA. These similarities tell scientists the genes in those regions play a critical role in cell function in both species, or they would have been lost during the 1 billion years of evolution that separate yeast and humans. About one-third of yeast genes are related to those in the human. Some of these critical processes include DNA copying and repair of damaged DNA, protein synthesis and transport across membranes, and control of metabolic processes. In cancer research, S. cerevisiae has emerged as an important model for studying control of the eukaryotic cell cycle.

Although yeast DNA shares many similarities with human DNA, finding yeast genes is easier because the yeast genome lacks the long stretches of filler DNA and repeated bases the human genome contains, which often cause scientists problems when examining a long DNA piece for the presence of genes.

Yet, scientists know the function of only half of the 6,000 genes the yeast sequencing effort has turned up. To understand what the others do will require systematic experiments that disable the genes and then determine what goes wrong in the yeast. Eventually, these experiments and others will give the world its first look at how a living cell functions as a unit.