deleterious mutation
Eyre-Walker A, Woolfit M & Phelps T 2006 The distribution of fitness effects of new deleterious amino acid mutations in humans. Genetics 173:891-900.
- we present a new method by which the distribution can be estimated
- the method is fairly robust to changes in population size and admixture
- it can be corrected for any residual effects if a model of the demography is available
- a gamma distribution with a shape parameter of 0.23 provides a good fit to the data
- >50% of mutations are likely to have mild effects
- they reduce fitness by between one one-thousandth and one-tenth
- <15% of new mutations are likely to have strongly deleterious effects
- on average a nonsynonymous mutation reduces fitness by a few percent
- the average strength of selection acting against a nonsynonymous polymorphism is ~9 × 10−5
- the relaxation of natural selection due to modern medicine and reduced variance in family size is not likely to lead to a rapid decline in genetic quality
- it will be very difficult to locate most of the genes involved in complex genetic diseases
- the method assumes that there is no dominance, epistasis, or advantageous mutation
- there is free recombination
- our method is likely to be seriously biased only if a large proportion of deleterious mutations are completely recessive
- or if mutations of very small effect tend to be recessive or dominant
