Search

Kuzmin, Elena; VanderSluis, Benjamin; Wang, Wen; Tan, Guihong; Deshpande, Raamesh; Chen, Yiqun; Usaj, Matej; Balint, Attila; Mattiazzi Usaj, Mojca; van Leeuwen, Jolanda; Koch, Elizabeth N.; Pons, Carles; Dagilis, Andrius Jonas; Pryszlak, Michael; Wang, Jason Zi Yang; Hanchard, Julia; Riggi, Margot; Xu, Kaicong; Heydari, Hamed; San Luis, Bryan-Joseph; Shuteriqi, Ermira; Zhu, Hongwei; Van Dyk, Nydia; Sharifpoor, Sara; Costanzo, Michael; Loewith, Robbie; Caudy, Amy; Bolnick, Daniel; Brown, Grant W.; Andrews, Brenda J.; Boone, Charles; Myers, Chad L. — 2019-03-30 To systematically explore complex genetic interactions, we constructed ~200,000 yeast triple mutants and scored negative trigenic interactions. We selected double-mutant query genes across a broad spectrum of biological processes, spanning a range of quantitative features of the global digenic interaction network and tested for a genetic interaction with a third mutation. Trigenic interactions often occurred among functionally related genes, and essential genes were hubs on the trigenic network. Despite their functional enrichment, trigenic interactions tended to link genes in distant bioprocesses and displayed a weaker magnitude than digenic interactions. We estimate that the global trigenic interaction network is ~100 times as large as the global digenic network, highlighting the potential for complex genetic interactions to affect the biology of inheritance, including the genotype-to-phenotype relationship.

Kuzmin, Elena; VanderSluis, Benjamin; Nguyen Ba, Alex N.; Wang, Wen; Koch, Elizabeth N.; Usaj, Matej; Khmelinskii, Anton; Mattiazzi Usaj, Mojca; van Leeuwen, Jolanda; Kraus, Oren; Tresenrider, Amy; Pryszlak, Michael; Hu, Ming-Che; Varriano, Brenda; Costanzo, Michael; Knop, Michael; Moses, Alan; L. Myers, Chad; Andrews, Brenda J.; Boone, Charles — 2020-08-05 <p>Whole-genome duplication<b> </b>has played a central role in genome evolution of many organisms, including the human genome. Most duplicated genes are eliminated and factors that influence the retention of persisting duplicates remain poorly understood. Here, we describe a systematic complex genetic interaction analysis with yeast paralogs derived from the whole-genome duplication event. Mapping digenic interactions for a deletion mutant of each paralog and trigenic interactions for the double mutant provides insight into their roles and a quantitative measure of their functional redundancy. Trigenic interaction analysis distinguishes two classes of paralogs, a more functionally divergent subset and another that retained more functional overlap. Gene feature analysis and modeling suggest that evolutionary trajectories of duplicated genes are dictated by combined functional and structural entanglement factors.</p>