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Home | Seminars and Symposia | Past seminars/symposia: Friday, November 17, 2006

The Biochemical Architecture of an Ancient Adaptive Landscape


Tony Dean
Biological Sciences

Friday, November 17, 2006
12:00 Lunch
12:15 Seminar

402 Walter Library The role of constraint in adaptive evolution is an open question. Directed evolution of an engineered isopropylmalate dehydrogenase (IMDH), with coenzyme specificity switched from NAD to NADP, always produces mutants with lower affinities for NADP. This result is the correlated response to selection for relief from NADPH inhibition expected of an adaptive landscape subject to three enzymatic constraints: an upper limit to, a correlation in NADP and NADPH affinities, and a trade-off between NAD and NADP usage. Two additional constraints, high intracellular NADPH abundance and the cost of compensatory protein synthesis, have ensured the conserved use of NAD by IMDH throughout evolution. Our results show that selective mechanisms and evolutionary constraints are to be understood in terms of underlying adaptive landscapes.