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

Introduction

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.

Research Model

To test this, my lab’s 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.

Originality of PLEIOTROPY

PLEIOTROPY’s originality is to contrast three types of species:

1. Ancestor-like molars (controls)
2. Derived molars that evolved either in line with pleiotropy constraints (higher crowns in both molars)
3. Derived molars that evolved 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.

Research Objectives

We will:

1. Compare how developmental gene expression in tooth germs evolves, and search for compensatory changes in developmental mechanisms. We will scan gene expression at spatial resolution in seven 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.

Conclusion

PLEIOTROPY exploits my unique expertise, examining genome evolution in connection with developmental evolution, to tackle the puzzling question of pleiotropy in evolution.