Leveraging the awesome power of Saccharomyces to probe the evolution of genetic networks.

Abstract

Causal loci for phenotypes of interest do not exist in isolation, but rather in complex, densely connected groups termed genetic interaction networks. Given the degree of functional conservation shared with humans, S. cerevisiae represents an excellent model organism for understanding the connection of genetic networks to complex traits. Within the field, questions remain about the conservation of genetic networks among various, distantly related species. To address this, I studied how functional rewiring has evolved in S. cerevisiae and its most distantly related Saccharomyces relative, S. uvarum. I used differential gene essentiality as my phenotype of interest, which was previously observed to occur for 12% of comparable orthologs. Differentially essential orthologs between S. cerevisiae and S. uvarum are capable of functional complementation, pointing towards changes in interaction partners as the genetic basis. My work focused on identifying these evolutionary changes in the genetic network between species by mapping these new interaction partners. Focusing on the differentially essential orthologs that are essential in S. cerevisiae only, for select candidate genes I leveraged the power of transposon mutagenesis and whole genome sequencing to perform genome wide reciprocal hemizygote screen in these hybrids to map loci with differential phenotypic results depending on the identity of the mutated parental allele. Analysis of transposon insertion rates across both parental genomes in the population will make it possible to identify novel genetic interaction partners that have been gained or lost for the non-essential S. uvarum ortholog. Mapping the genetic network changes among these two 20 mya diverged Saccharomyces yeasts will provide new insight into the level of conservation across the Eukaryotic tree of life.