Research SummaryDecoding Organism-Related Evolution of Survivin, a Hub Protein
Natural selection spreads the beneficial genotypes but the processes that create and maintain genotypic diversity to select from, even in the absence of selection pressure, are also of paramount importance and in true sense decide the limits of biological evolution. Biological complexity, robustness and evolvability have long been debated for such contribution in evolution; however scarcity of experimental data eluded a clear understanding. I will experimentally uncover their interrelationship at the level of protein using “survivin”, a hub protein. Using interactome size of survivin as a proxy of complexity, I will investigate its effect on (i) robustness against point mutations and (ii) the capacity to gain/lose interaction(s) (proxy for evolvability). As regards of (i), fitness landscape of survivin, containing fitness information on all the possible point mutations, will be captured and robustness will be measured from neutral mutations. As regards of (ii) binding landscapes of survivin, containing information of the effect of mutations on binding to various interaction partners will be captured. Additionally, to develop mechanistic understanding of interrelationship between complexity, robustness and evolvability on a structural framework, crystal structures of few of the selected survivin mutants alone and in complex with binding partners will be acquired.
Figure Legend: The scheme depicts the primary goals and approaches of the proposed work. The green arrows indicate the accepted relationship between complexity, robustness and evolvability of biological systems.