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DENOVOMUT SIGNED

An integrated approach to understanding the impact of de novo mutations on the mammalian genome

Total Cost €

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EC-Contrib. €

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Partnership

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Project "DENOVOMUT" data sheet

The following table provides information about the project.

Coordinator
THE UNIVERSITY OF EDINBURGH 

Organization address
address: OLD COLLEGE, SOUTH BRIDGE
city: EDINBURGH
postcode: EH8 9YL
website: www.ed.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Total cost 2˙499˙331 €
 EC max contribution 2˙499˙331 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-AdG
 Funding Scheme ERC-ADG
 Starting year 2017
 Duration (year-month-day) from 2017-01-01   to  2021-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    THE UNIVERSITY OF EDINBURGH UK (EDINBURGH) coordinator 1˙816˙709.00
2    MAX-PLANCK-GESELLSCHAFT ZUR FORDERUNG DER WISSENSCHAFTEN EV DE (MUENCHEN) participant 682˙621.00

Map

 Project objective

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.

 Publications

year authors and title journal last update
List of publications.
2017 Tom R. Booker, Benjamin C. Jackson, Peter D. Keightley
Detecting positive selection in the genome
published pages: , ISSN: 1741-7007, DOI: 10.1186/s12915-017-0434-y
BMC Biology 15/1 2020-01-28
2018 Peter D. Keightley, Benjamin C. Jackson
Inferring the Probability of the Derived versus the Ancestral Allelic State at a Polymorphic Site
published pages: genetics.301120., ISSN: 0016-6731, DOI: 10.1534/genetics.118.301120
Genetics 2020-01-28
2017 Tom R. Booker, Rob W. Ness, Peter D. Keightley
The Recombination Landscape in Wild House Mice Inferred Using Population Genomic Data
published pages: 297-309, ISSN: 0016-6731, DOI: 10.1534/genetics.117.300063
Genetics 207/1 2020-01-28

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