Objectif Understanding the process of spontaneous mutation is fundamental for understanding the genetic basis of quantitative variation, the threat posed by declining population size in conservation biology and the distribution of nucleotide variation in the genome. I will address these and other unanswered questions concerning the evolutionary impact of spontaneous mutation using the house mouse as a model system. With the first, highly replicated mutation accumulation (MA) experiment in any vertebrate, I will study the impact of mutation accumulation on fitness and other quantitative traits and on genomic variation. I will pay particular attention to the effects of mutations in the heterozygous state, since this is important for resolving two important questions: 1. The threat posed by deleterious mutation accumulation in humans, where natural selection has weakened in many populations, and in endangered species, where declining effective population size has made selection less effective, and 2. The extent by which new mutations sustain response to artificial selection. By characterizing many thousands of mutation events by genome sequencing of MA lines and wild mice, I will determine the molecular spectrum and the factors explaining mutation rate variation across the genome. I will exploit this new knowledge to address the long-unanswered question of the causes of correlations between nucleotide diversity and the recombination rate and the density of conserved genomic elements. I will develop new approaches, incorporating the simultaneous action of mutation, selection, drift and recombination, to determine the contributions of background selection and selective sweeps to variation in nucleotide diversity, and to quantify the contributions of coding and noncoding mutations to fitness variation. The project will lead to substantial advances in the understanding of the role of new mutations in explaining phenotypic and molecular diversity in mammals. Champ scientifique natural sciencesbiological sciencesevolutionary biologynatural sciencesbiological sciencesgeneticsmutationnatural sciencesbiological sciencesgeneticsnucleotidesnatural sciencesbiological scienceszoologymammalogynatural sciencesbiological sciencesgeneticsgenomes Mots‑clés DENOVOMUT Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Thème(s) ERC-ADG-2015 - ERC Advanced Grant Appel à propositions ERC-2015-AdG Voir d’autres projets de cet appel Régime de financement ERC-ADG - Advanced Grant Institution d’accueil THE UNIVERSITY OF EDINBURGH Contribution nette de l'UE € 1 680 706,72 Adresse OLD COLLEGE, SOUTH BRIDGE EH8 9YL Edinburgh Royaume-Uni Voir sur la carte Région Scotland Eastern Scotland Edinburgh Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 680 706,72 Bénéficiaires (2) Trier par ordre alphabétique Trier par contribution nette de l'UE Tout développer Tout réduire THE UNIVERSITY OF EDINBURGH Royaume-Uni Contribution nette de l'UE € 1 680 706,72 Adresse OLD COLLEGE, SOUTH BRIDGE EH8 9YL Edinburgh Voir sur la carte Région Scotland Eastern Scotland Edinburgh Type d’activité Higher or Secondary Education Establishments Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 1 680 706,72 MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV Allemagne Contribution nette de l'UE € 818 624,28 Adresse HOFGARTENSTRASSE 8 80539 Munchen Voir sur la carte Région Bayern Oberbayern München, Kreisfreie Stadt Type d’activité Research Organisations Liens Contacter l’organisation Opens in new window Site web Opens in new window Participation aux programmes de R&I de l'UE Opens in new window Réseau de collaboration HORIZON Opens in new window Coût total € 818 624,28