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

Summary
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 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.PLEIOTROPY’s 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
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More information & hyperlinks
Web resources: https://cordis.europa.eu/project/id/101088398
Start date: 01-12-2023
End date: 30-11-2028
Total budget - Public funding: 1 992 395,00 Euro - 1 992 395,00 Euro
Cordis data

Original description

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 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.PLEIOTROPY’s 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

Status

SIGNED

Call topic

ERC-2022-COG

Update Date

31-07-2023
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Horizon Europe
HORIZON.1 Excellent Science
HORIZON.1.1 European Research Council (ERC)
HORIZON.1.1.0 Cross-cutting call topics
ERC-2022-COG ERC CONSOLIDATOR GRANTS
HORIZON.1.1.1 Frontier science
ERC-2022-COG ERC CONSOLIDATOR GRANTS