The Functional Basis of Genetic Interactions Underlying Quantitative Trait Variation

New York University, New York NY

Investigators

Abstract

Intellectual Merit Most inherited traits are quantitative and determined by variation in multiple genes dispersed throughout the genome. Genetic variation in these different genes can interact in ways that are difficult to predict. The project aims to identify principles governing relationships between genes that underlie quantitative trait variation. This project will study genetic interactions in a model experimental system for naturally occurring quantitative trait variation and identify general principles regarding the functional relationships between interacting genes. The research entails selecting yeast mutants that have increased cell growth rates by performing evolution experiments in carefully defined environments. Experiments will be designed so that mutants accumulate a small number of mutations relative to the founding strain. This project will identify all the acquired genetic variation using whole genome resequencing and construct a panel of strains carrying individual mutations and all possible combinations of mutations. It will quantify growth rates for each genotype combination and determine the nature of the interactions between the gene variants. It will then study the functional relationships between genes that interact in different ways using the extensive functional annotation available for the yeast genome. Just as genes and their products are conserved across the kingdoms of life, interactions between genes, and the principles that govern the outcome of those interactions, are likely to be conserved. Thus, findings from the study will inform our understanding of the genetic architecture of quantitative traits in model and non-model organisms. Broader Impacts The project will contribute to an understanding of how genes interact with potential applications to improving agricultural breeding practices. This work will have a number of broader impacts in undergraduate and science education, inclusion of underrepresented groups, and enhancement of scientific understanding. The project will include undergraduates, underrepresented minorities and students from primarily undergraduate institutions. It will involve training scientists in genetics, computational biology and microbiology at the graduate and undergraduate level. In addition, the project will include an outreach program that provides high school students with the opportunity to work in a laboratory environment. High school students from diverse backgrounds will be provided with training in experimental and computational biology and undertake an independent research project in the laboratory. The project will provide mentorship so that high school students can submit their research to national science competitions. Concomitant with the proposed project, a new integrative course for undergraduate students will be developed that combines instruction in statistics, genetics and computing.