Towards mechanistic and predictive understanding of evolution
Knowing how changes in genotype alter phenotype is critical for understanding evolution. Furthermore, once you know the effects of mutations and the interactions between them, the outcomes of evolution become at least somewhat predictable. This is why so much effort has been put into describing genotype-phenotype maps. And yet, almost all such studies are observational in their nature: they characterize the effects of mutations without understanding the underlying causes that determine them. Without such causal understanding, predicting evolution is limited only to the systems with experimentally characterized genotype-Phenotype maps. In this talk, I will present several attempts we have made in recent years to describe how existing molecular mechanisms in bacterial cells determine genotype-phenotype mapping. In particular, I will show how knowing the biophysical mechanisms that govern protein-DNA binding allows us to predict the effects of mutations in bacterial promoters and the epistatic interactions between them.