PLEIOTROPY · Evaluating how pleiotropy influences genetic and developmental evolution by using rodent teeth

Pleiotropy is the phenomenon of one gene affecting several phenotypic traits, such as different organs. Mutations advantageous in one organ often have antagonistic effects in others. Recent theoretical and empirical data suggest adaptation proceeds with such pleiotropic mutations if they are compensated during development. I think that pleiotropy may promote the fast divergence of developmental gene expression and cis-regulatory regions while selecting for such compensations.To test this, my labs model, the upper and lower molars in rodents, will be ideal to: -Link variation in genes, development and shape, and track compensations in developmental processes. -Focus on a tractable case of pleiotropy with two organs. -Compare the evolution for different pleiotropy constraints. We have established a collection of rodents and methods to compare their genomes and developing molars.PLEIOTROPYs originality is to contrast 3 types of species: Ancestor-like molars (controls), and derived molars that evolved either in line with pleiotropy constraints (higher crowns in both molars), or against them (extra cusps only in the upper molar). Our hypothesis implies that gene expression and cis-regulatory regions evolve faster in the latter case. We will: 1) Compare how developmental gene expression in tooth germs evolve, and search for compensatory changes in developmental mechanisms. We will scan gene expression at spatial resolution in 7 focal species. 2) Survey how regulatory regions evolve, and test compensatory mutations. We will annotate regulatory regions from epigenomic data and infer their phylogenetic history in 67 species. We will screen and validate compensatory mutations. 3) Model the joint evolution of upper and lower molars development to predict rates of genome evolution and compensatory mutations.PLEIOTROPY exploits my unique expertise, examining genome evolution in connection with developmental evolution, to tackle the puzzling question of pleiotropy in evolution