Dave Anderson
Senior Instructor
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Ph.D. (Doctor of Philosophy)
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Research and teaching
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I am interested in the intersection between molecular functions, biochemistry and evolution; basically, I want to know about the molecular mechanisms that underlie important evolutionary innovations. I am focused on the ways in which physical interactions between mutations at different sites (i.e. epistasis) govern the set of evolutionary pathways that are available to a given protein at a given point in its evolutionary history. To investigate this, I have developed a suite of different statistical analysis tools that estimate the effect of distinct mutations on a single quantitative function, which allows for the simultaneous assessment of potential molecular interactions between them.
Some examples of my projects include the functional origins of the methyl-parathion hydrolase (MPH) enzyme from its dihydrocoumarin hydrolase (DHC) ancestor, the mechanisms of incompatibility in a set of engineered phosphotriesterases, and the functional diversification of the steroid receptor DNA-binding domains. I am always open to applying these tools and approaches to new systems, and assessing how generally epistasis governs evolutionary trajectories.
Figure legend: Two alternate trajectories for evolving greater phosphotriesterase from the same genotypic starting point. The optimal trajectory (purple) is defined by an initial Histidine->Arginine mutation, while the sub-optimal trajectory (cyan) is defined by an initial Histidine->Serine change. At first, the sub-optimal trajectory can still access the optimal trajectory (green edges) before becoming separated by a deleterious valley (red edges). Grey surfaces indicate logarithmic scale of catalytic activity.