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Project

Systematic perturbation and adaptive evolution to understand the genetic basis of complex traits

A complex genetic trait arises out of the contributions and interactions of several pathways and protein complexes. Global genetic analyses have identified the major components of many complex genetic traits, but constructing a more integrative view of such traits remains a major challenge. In this research proposal, we will use a novel approach to study the architecture and adaptive potential of a complex trait by experimental evolution. Using oxidative stress resistance as a model trait, we will systematically characterize the compensatory potential of the model eukaryote Saccharomyces cerevisiae after gene loss. Oxidative stress resistance is a variable trait in yeast and is of industrial and clinical importance. First, Bar-Seq experiments under oxidative stress conditions will be used to identify genes that are important for growth under these conditions. We will make deletions of the selected genes in a clean background and use high-throughput phenotypic screens to look at the pleiotropic effects of the gene loss. Then the deletion strains will be allowed to adapt to growth under oxidative stress by experimental evolution. To investigate the adaptive routes in the evolved lineages, we will characterize the strains by whole-genome and RNA sequencing. The resulting large-scale dataset will be analysed through advanced bioinformatics, and then exploited to develop quantitative models of oxidative stress resistance. Finally, the developed model will be applied to feral yeast strains to test its potential to predict oxidative stress resistance. In essence, through systematic perturbation and adaptive evolution we will advance our understanding of the chosen complex trait by showing how the different component s can interact to compensate for the loss of a component.
Date:1 Oct 2016 →  30 Sep 2021
Keywords:genetics
Disciplines:Plant biology