A Novel Role of the N Terminus of Budding Yeast Histone H3 Variant Cse4 in Ubiquitin-Mediated Proteolysis |
| |
Authors: | Wei Chun Au Anthony R. Dawson David W. Rawson Sara B. Taylor Richard E. Baker Munira A. Basrai |
| |
Affiliation: | *Genetics Branch Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20889;†Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts 01655 |
| |
Abstract: | Understanding the molecular basis of common traits is a primary challenge of modern genetics. One model holds that rare mutations in many genetic backgrounds may often phenocopy one another, together explaining the prevalence of the resulting trait in the population. For the vast majority of phenotypes, the role of rare variants and the evolutionary forces that underlie them are unknown. In this work, we use a population of Saccharomyces paradoxus yeast as a model system for the study of common trait variation. We observed an unusual, flocculation and invasive-growth phenotype in one-third of S. paradoxus strains, which were otherwise unrelated. In crosses with each strain in turn, these morphologies segregated as a recessive Mendelian phenotype, mapping either to IRA1 or to IRA2, yeast homologs of the hypermutable human neurofibromatosis gene NF1. The causal IRA1 and IRA2 haplotypes were of distinct evolutionary origin and, in addition to their morphological effects, associated with hundreds of stress-resistance and growth traits, both beneficial and disadvantageous, across S. paradoxus. Single-gene molecular genetic analyses confirmed variant IRA1 and IRA2 haplotypes as causal for these growth characteristics, many of which were independent of morphology. Our data make clear that common growth and morphology traits in yeast result from a suite of variants in master regulators, which function as a mutation-driven switch between phenotypic states. |
| |
Keywords: | Cse4 Psh1 ubiquitin-mediated protein degradation Doa1 chromosome segregation |
|
|