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Science at the Edge Seminar

Speaker:  Michael Harms, Institute of Molecular Biology and Department of Chemistry & Biochemistry, University of Oregon

Title: Biophysics of Protein Evolution

Refreshments at 11:15 am.

Date: Fri, 07 Sep 2018, 11:30 am – 12:30 pm
Type: Seminar
Location: 1400 BPS Bldg.

How does protein bio­chemistry shape protein evolu­tion? How do new bio­chemical fea­tures evolve? To answer these ques­tions, the Harms lab studies protein evolu­tion using phylo­genetic analy­ses, compu­ta­tional and experi­mental studies of pro­tein “se­quence space”, and rigor­ous studies of pro­tein bio­chemistry. I will dis­cuss two on­going projects. In the first, we ask the decep­tively sim­ple ques­tion: why can't we pre­dict the com­bined ef­fect of muta­tions by sum­ming their indi­vidual effects? Through a set of compu­ta­tional and experi­mental studies, we demon­strate that uni­versal thermo­dynamic con­sidera­tions ex­plain why muta­tions do not com­bine additive­ly. In­spired by these re­sults, we are develop­ing quan­tita­tive, mechan­istic models to ac­count for non-additiv­ity be­tween muta­tions—poten­tially leading to pre­dictive models of pro­tein evolu­tion. In the second project, we are in­vesti­gating the evolu­tion of the in­nate im­mune protein S100A9. This protein can exist as either a pro-inflam­matory homo­dimer or as an anti­micro­bial hetero­dimer with the protein S100A8. We found that the hetero­dimer arose from an ancient homo­meric inter­face that was main­tained after gene duplica­tion. The key histori­cal muta­tions that con­ferred inflam­matory and anti­micro­bial activity have dif­ferent effects when intro­duced into the homo­dimer versus the hetero­dimer. This allowed a small protein to ac­quire new func­tions with­out com­promising exis­ting func­tions. We sus­pect this may be a general mode by which multi­func­tional protein evolve.