Molecular mechanisms controlling complex traits in yeast

Abstract

A fundamental goal in biology is to understand how the information stored in DNA results in a cellular function. However, it is insufficient to study one variant of a particular DNA sequence because most people do not share identical genome sequences, and the differences in DNA sequence have functional consequences. In this thesis, I examine how natural variation in the Saccharomyces cerevisiae genome can affect cellular processes. This is done using deletion libraries to examine how mutations in the same gene but in two different genetic backgrounds of S. cerevisiae, S288c and [summation]1278b, can lead different phenotypes for two traits: gene essentiality and agar adhesion. We found that the genomes of the S288c and [summation]1278b strains are only as divergent as two humans in the population. However, analyses of deletion libraries in each strain revealed 57 genes have functions that are essential in one strain but not the other. Strain specific phenotypes are more pronounced for the trait of agar adhesion where 553 deletions have phenotypes that are specific to one strain or the other. Part of the difference is because the [summation]1278b strain requires the filamentation mitogen activated kinase pathway (fMAPK) for agar adhesion but the S288c strain does not. I found that S288c is able to bypass the fMAPK pathway because it contains an allele of the transcription factor RPI1 that promotes transcription of the gene FLO11. Characterization of the sequence differences between the S288c and 11278b alleles of RPIJ revealed that they differ in the number of intragenic tandem repeats. Examination of the genomes of both strains uncovered the possibility that expansions and contractions of intragenic repeats may be a general mechanism to quickly introduce genomic and phenotypic variation.