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Sex-specific genetic effects on fitness and human disease

Objective

Darwin’s theory of natural selection rests on the principle that fitness variation in natural populations has a heritable component, on which selection acts, thereby leading to evolutionary change. A fundamental and so far unresolved question for the field of evolutionary biology is to identify the genetic loci responsible for this fitness variation, thereby coming closer to an understanding of how variation is maintained in the face of continual selection. One important complicating factor in the search for fitness related genes however is the existence of separate sexes – theoretical expectations and empirical data both suggest that sexually antagonistic genes are common. The phrase “two sexes, one genome” nicely sums up the problem; selection may favour alleles in one sex, even if they have detrimental effects on the fitness of the opposite sex, since it is their net effect across both sexes that determine the likelihood that alleles persist in a population. This theoretical framework raises an interesting, and so far entirely unexplored issue: that in one sex the functional performance of some alleles is predicted to be compromised and this effect may account for some common human diseases and conditions which show genotype-sex interactions. I propose to explore the genetic basis of sex-specific fitness in a model organism in both laboratory and natural conditions and to test whether those genes identified as having sexually antagonistic effects can help explain the incidence of human diseases that display sexual dimorphism in prevalence, age of onset or severity. This multidisciplinary project directly addresses some fundamental unresolved questions in evolutionary biology: the genetic basis and maintenance of fitness variation; the evolution of sexual dimorphism; and aims to provide novel insights into the genetic basis of some common human diseases.

Call for proposal

ERC-2011-StG_20101109
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Host institution

THE UNIVERSITY OF SUSSEX
Address
Sussex House Falmer
BN1 9RH Brighton
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 1 500 000
Principal investigator
Edward Hugh Morrow (Dr.)
Administrative Contact
Liane Wrigg (Ms.)

Beneficiaries (1)

THE UNIVERSITY OF SUSSEX
United Kingdom
EU contribution
€ 1 500 000
Address
Sussex House Falmer
BN1 9RH Brighton
Activity type
Higher or Secondary Education Establishments
Principal investigator
Edward Hugh Morrow (Dr.)
Administrative Contact
Liane Wrigg (Ms.)