Characterizing the Genotype-Phenotype Map and Its Evolution: A Radically New Strategy

Tuesday, November 17, 2015 - 9:00am - 10:00am
Keller 3-180
Michael Savageau (University of California)
Although we now have a generic concept of ‘genotype’ provided by the detailed DNA sequence, there is no corresponding generic concept of ‘phenotype’. Without a generic concept of phenotype there can be no rigorous framework for a deep understanding of the complex biochemical systems that link genotype to phenotype. I will describe advances in a novel “design space” approach that addresses this important challenge by providing a generic definition of phenotype and automatically identifying the corresponding subsystems. The qualitatively distinct phenotypes of a complex system can then be rigorously defined and counted, their fitness analyzed and compared, their global tolerances measured, and their biological design principles revealed. The boundaries between phenotypes in design space are defined by the system itself. Thus, they provide an objective scale that distinguishes “small” from “large” mutant effects and thereby a resolution of the apparent robustness/evolvability paradox. A few simple applications will be used to illustrate how this approach elucidates the relationship between genotypically determined parameters, environmentally determined variables, and the qualitatively distinct phenotypes of biological systems. This approach provides a quantitative understanding of evolution for a number of natural systems, and a global perspective on the phenotypic repertoire that facilitates the directed evolution of synthetic gene circuits.