Complex genetic interaction network rewiring and dynamics

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Whole-genome duplication (WGD) events are pervasive in eukaryotes, shaping the genomes of simple single-celled organisms, such as yeast, as well as those of more complex metazoans, including humans. Most duplicated genes are eliminated after WGD because one copy accumulates deleterious mutations, leading to its loss. However, a significant proportion of duplicates persists, and factors that result in duplicate gene retention are poorly understood but critical for understanding the evolutionary forces that shape genomes. In yeast, whole genome duplication appears to have occurred approximately 100 Mya after the divergence of Kluyveromyces from Saccharomyces lineages and around the time of the emergence of angiosperms (flesh fruit plants) resulting in changes to their metabolic milieu. Quantifying the functional divergence of paralog pairs is of particular interest because of the strong selection against functional redundancy. Complex genetic interaction analysis has been effectively used to assess the functional relationship of duplicated genes. The goal of the proposed program is to develop a theoretical and practical framework to relate genotype-to-phenotype and genetic wiring to genome evolution, by studying how complex genetic interaction networks are modulated by environmental changes resulting in duplicated gene retention. First, we will quantify single and double mutant fitness of WGD duplicated on metabolic conditions. Second, we will map the conditional complex genetic interaction network of duplicated genes. Third, we will measure conditional trigenic interactions to define conditional functional redundancy and divergence of duplicated genes. This comprehensive network of conditional complex genetic interactions of duplicated genes will reveal mechanisms of duplicated gene retention in yeast, the evolution of conditional functional divergence of duplicated genes and help us to functionally annotate the yeast genome thereby providing insight into the genotype-to-phenotype relationship.