Human Genome Project Reaches Major Goal
An international consortium of scientists announced at the end of April that they had achieved a major goal of the Human Genome Project the complete sequence of a eukaryote, the single-celled Saccharomyces cerevisiae strain S288C. The 16 yeast chromosomes were sequenced from tip to tip with no gaps, and both strands of the DNA double helix were analyzed, resulting in an accuracy rate higher than 99.99%. The biggest surprise of the project was that more than half the genes uncovered during sequencing were previously unknown, despite decades of intense scrutiny by yeast geneticists. Another unexpected discovery was the degree of redundancy in the genome, with several genes often appearing to have homologous sequences and functions.
The full yeast sequence has been publicly available since the end of April, but access formerly was limited to the laboratories involved in the sequencing project, those in the follow-up functional analysis program (Eurofan), and companies in the Yeast Industry Platform, Brussels.
With some 12 million base pairs and 6000 genes, the eukaryotic (nucleus-containing) yeast has already provided biologists with a valuable resource for determining the function of individual human genes involved in such medical problems as cancer, neurological disorders, and skeletal disorders. "Now we know for the first time all the genes it takes to make a simple eukaryotic cell," said Mark Johnston [Washington University, St. Louis (WUSL)]. "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 [a more complex eukaryotic organism] can be deduced through experiments with yeast, which is much more amenable to genetic manipulation."
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 function as an integrated cell system.
The quest to interpret the yeast genome began in the 1950s when Robert Mortimer (University of California, Berkeley) began genetic mapping of all the organism's genes. In the early 1980s, Maynard Olson (then at WUSL) created a physical map of the yeast genome by cloning overlapping DNA fragments. This map provided the starting point for the sequencing phase, which was initiated in 1989 when Andre Goffeau (Catholic University of Louvain-La-Neuve, Belgium) organized a group of European laboratories to take on the task.
As part of the Human Genome Project, laboratories applied large-scale automation, helping to finish the work some 2 years sooner than the scientists themselves had predicted.
The project, which cost about $30 million, involved more than 100 laboratories in the European Union (EU), 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 Goffeau, who coordinated the 70-laboratory EU initiative. "We agreed not to stake out any territory and, on several occasions, DNA fragments to be sequenced were redistributed according to the respective capabilities of the sequencing teams." Europeans sequenced 55% of the genome; the Sanger Centre, 17%; WUSL, 15%; Stanford University, 7%; McGill University in Canada, 4%; and the Institute of Physical and Chemical Research (RIKEN) in Japan, 2%.
Sanger Centre and Institut Pasteur are now sequencing Mycobacterium tuberculosis with support from The Wellcome Trust. |
