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Genetics, Vol. 167, 1109-1121, July 2004, Copyright © 2004
doi:10.1534/genetics.104.029256

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Defects Arising From Whole-Genome Duplications in Saccharomyces cerevisiae

Alex A. Andalis*, Zuzana Storchova{dagger}, Cora Styles*, Timothy Galitski*,1, David Pellman{dagger} and Gerald R. Fink*,2

* Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142
{dagger} Department of Pediatric Oncology of The Dana-Farber Cancer Institute, Department of Pediatric Hematology/ Oncology of the Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115

2 Corresponding author: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142.
E-mail: gfink{at}wi.mit.edu

Comparisons among closely related species have led to the proposal that the duplications found in many extant genomes are the remnants of an ancient polyploidization event, rather than a result of successive duplications of individual chromosomal segments. If this interpretation is correct, it would support Ohno's proposal that polyploidization drives evolution by generating the genetic material necessary for the creation of new genes. Paradoxically, analysis of contemporary polyploids suggests that increased ploidy is an inherently unstable state. To shed light on this apparent contradiction and to determine the effects of nascent duplications of the entire genome, we generated isogenic polyploid strains of the budding yeast Saccharomyces cerevisiae. Our data show that an increase in ploidy results in a marked decrease in a cell's ability to survive during stationary phase in growth medium. Tetraploid cells die rapidly, whereas isogenic haploids remain viable for weeks. Unlike haploid cells, which arrest growth as unbudded cells, tetraploid cells continue to bud and form mitotic spindles in stationary phase. The stationary-phase death of tetraploids can be prevented by mutations or conditions that result in growth arrest. These data show that whole-genome duplications are accompanied by defects that affect viability and subsequent survival of the new organism.




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