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University of Massachusetts Medical School Faculty Publications

Evolution

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Full-Text Articles in Molecular Biology

Pervasive Contingency And Entrenchment In A Billion Years Of Hsp90 Evolution, Tyler N. Starr, Julia Flynn, Parul Mishra, Daniel N. Bolon, Joseph W. Thornton Jan 2018

Pervasive Contingency And Entrenchment In A Billion Years Of Hsp90 Evolution, Tyler N. Starr, Julia Flynn, Parul Mishra, Daniel N. Bolon, Joseph W. Thornton

University of Massachusetts Medical School Faculty Publications

Interactions among mutations within a protein have the potential to make molecular evolution contingent and irreversible, but the extent to which epistasis actually shaped historical evolutionary trajectories is unclear. We addressed this question by identifying all amino acid substitutions that occurred during the billion-year evolutionary history of the heat shock protein 90 (Hsp90) ATPase domain beginning from a deep eukaryotic ancestor to modern Saccharomyces cerevisiae and then precisely measuring their fitness effects when introduced into both extant and reconstructed ancestral Hsp90 proteins. We find a pervasive influence of epistasis: of 98 derived states that evolved during history, most were deleterious ...


A Systematic Survey Of An Intragenic Epistatic Landscape, Claudia Bank, Ryan T. Hietpas, Jeffrey D. Jensen, Daniel N. Bolon Oct 2014

A Systematic Survey Of An Intragenic Epistatic Landscape, Claudia Bank, Ryan T. Hietpas, Jeffrey D. Jensen, Daniel N. Bolon

University of Massachusetts Medical School Faculty Publications

Mutations are the source of evolutionary variation. The interactions of multiple mutations can have important effects on fitness and evolutionary trajectories. We have recently described the distribution of fitness effects of all single mutations for a nine amino acid region of yeast Hsp90 (Hsp82) implicated in substrate binding. Here, we report and discuss the distribution of intragenic epistatic effects within this region in seven Hsp90 point mutant backgrounds of neutral to slightly deleterious effect, resulting in an analysis of more than 1000 double-mutants. We find negative epistasis between substitutions to be common, and positive epistasis to be rare – resulting in ...