Evaluating how pleiotropy influences genetic, developmental and morphological evolution by using rodent teeth – PLEIOTROPY

Pleiotropy is the phenomenon of one gene affecting several phenotypic traits, such as different organs. When these organs evolve, what happens to the pleiotropic genes underlying their development? We think it triggers fast molecular evolution, because mutations with negative pleiotropic effects are counterbalanced by compensatory mutations.
To test this hypothesis we need to : -Link variation in genes, development and morphology, because compensations arise at the level of developmental processes. -Focus on a tractable case of pleiotropy with two organs. -Compare the rate and mode of evolution for different pleiotropy constraints. My lab’s model, the upper and lower molars in rodents, meets these conditions. We have established a collection of rodents and methods to compare their genomes and developing molars. PLEIOTROPY’s originality is to contrast 3 types of species: Controls, with molars similar to the ancestor. Coupled, with higher crowns evolving in both molars, in line with pleiotropy constraints. Decoupled, with supplementary cusps evolving in the upper molar only, against pleiotropy constraints. By comparing these 3 types we will : 1) Survey how developmental regulations in tooth germs evolve, and search for compensatory changes in developmental mechanisms. We will compare cellular composition and cellular gene expression in 6 species 2) Survey how coding and regulatory regions evolve, and search for compensatory mutations. We will compare sequences of hundreds of genes associated with molar development in 84 species 3) Model the joint evolution of upper and lower molars development to predict the effect of pleiotropy and test compensatory mutations before functional validation. PLEIOTROPY exploits my unique expertise, examining genome evolution in strong connection with developmental evolution. We will tackle an essential question in development and evolutionary biology: How do shape, development and genome evolve despite pleiotropic constraints.