deleterious mutation
Loewe L & Hill WG 2010 The population genetics of mutations: good, bad and indifferent. Phil Trans R Soc Lond B 365:1153-1167.
- many advances in the past built on models that treat the evolution of mutations at each DNA site independently
- neglecting linkage of sites on chromosomes and interactions of effects between sites (epistasis)
- we review work that addresses these limitations, to predict how mutations interfere with each other
- (i) the effects of mutations often depend on the presence or absence of other mutations
- (ii) their effects can also depend on the environment
- (iii) the fate of mutations may depend on the size and structure of the population
- (iv) mutations' fate can also depend on the fate of others that have more pronounced effects and are in close proximity on the same chromosome
- experimental approaches for inferring DMEs are based on mutation accumulation experiments pioneered by Mukai in Drosophila
- their strength is in the direct observation of the consequences of mutations that have relatively large effects of around 1 per cent
- they require great care to control for potential confounding factors
- mutations of small effects cannot be detected
- many researchers have recently used population genetics models and DNA sequence data to infer DMEs
- such DME estimates are most reliable for slightly deleterious mutational effects
- divergence among unselected lines has tended to increase more slowly than neutral predictions
- such a plateau can occur because there is a limited potential number of functional alleles and no new useful mutations occur
- or because back mutations dominate
- or because fitness effects are limiting, e.g. segregating mutants with highly deleterious pleiotropic effects on fitness
