2002 GSA Honors and Awards

Why I Developed the Yeast Genetic Map

IN the late 1940s while finishing my degree as an honors physics major at the University of Alberta, I decided to look for future options. Fortunately, UA had a good library where I discovered the program in biophysics at the University of California, Berkeley. I wrote to Professor Cornelius Tobias, advisor of the program, and was accepted as a Ph.D. candidate with a teaching assistantship. Meanwhile, I had begun doing geophysical work with an oil survey company in Calgary at a time when large reservoirs of oil were being discovered in Alberta. The oil industry offered an adventuresome and lucrative future.

However, I opted for UC Berkeley and was married; together we headed south where I joined Tobias, who was working with Raymond Zirkle, professor at the University of Chicago, trying to determine if haploid cells were more or less resistant to ionizing radiation than diploid cells. The diploids were more resistant. Zirkle and Tobias constructed a recessive lethal model to explain this difference. To test their model I constructed and tested triploid and tetraploid cells, which, contrary to their model that predicted that they should be more resistant, became progressively more sensitive. After perusing the biology library at Berkeley regarding radiobiology and ploidy, I found that there was much to learn about the field. Subsequently, my interests focused on the area of dominant lethality, and after further research, I proposed a theory to explain the higher sensitivity in tetraploid cells: the damage was partially caused by dominant lethality, which resulted from chromosome aberrations whose frequencies increased with the ploidy of the irradiated cell. Such damage was then demonstrated in haploid and diploid irradiated cells in yeast, thus confirming my hypothesis.

The theories of dominant lethality involved chromosome aberrations and the formation of dicentric chromosomes that formed anaphase bridges. These bridges led to mechanical disruption of mitosis, which led me to try to demonstrate chromosome abberations in yeast. Yeast chromosomes were small and not subject to cytological examination so I decided to develop the yeast genetic map that I hoped could facilitate further characterization of the chromosomes. The Neurospora and Aspergillus maps had already been developed, showing that their chromosome numbers were small, 7 or 8. Additionally, Perkins had published articles describing a genetic method to detect Neurospora chromosome aberrations. I reasoned that yeast, also being a fungus, should have a similar number. I planned to take a year off to develop this map of yeast but it turned out to be a much bigger job.

In 1960 Don Hawthorne and I published our first article on yeast genetic mapping in GENETICS. It is my view that this was a seminal article in yeast genetics research that proved to lay a cornerstone for the entire field of yeast genetics research. It not only defined a number of centromere-linked genes and their associated centromeres and provided the framework map on which others could build, but also laid out clearly the way to map genes and chromosomes using unordered tetrads. It was eventually discovered that yeast had 16 chromosomes and the recombination along each of these chromosomes was high. Subsequently, I continued mapping in collaboration with other investigators until, 40 years later when the job was nearly finished, I turned the project over to David Botstein of Stanford University, for publication of the twelfth edition of the yeast genetic map. Completion of the yeast genome sequence soon followed.

I am pleased to have spent a good part of my career helping develop yeast as a model organism, which has become widely used in laboratories doing research in many fields, including detection of human diseases.