deleterious mutation

Hedrick PW 1994 Purging inbreeding depression and the probability of extinction: full-sib mating. Heredity 73:363-372.

  • Templeton & Read (1984) suggested that 'inbreeding depression can be rapidly and effectively reduced by an appropriate breeding program'
  • their approach has been interpreted to mean that deliberate inbreeding may be used to purge a population of lethals or other genes causing inbreeding depression
  • population genetics theory predicts that the frequency of recessive lethals would be lower in a population that has had a low population size in the past than in a larger population (Lande & Barrowclough, 1987)
  • genetic variation at other loci may be greatly reduced during the purging period because of the reduction of the effective population size
  • so that the future potential for adaptation in the population may be lost
  • the advantages of eliminating a large part of the genetic load in a short period of time may be outweighed either by the potential cost from a higher risk of immediate or long-term extinction or from increased future risk in loss of adaptive potential
  • the lethals appear to be nearly completely recessive while the detrimental alleles have a substantial effect in heterozygotes
  • the detrimentals are not as recessive as the lethals
  • the incidence of recessive genetic diseases is lower in some South Indian human populations that historically have had higher rates of consanguineous marriages
  • inbreeding depression may also be expressed through other fitness components
  • such as male mating ability
  • or female fecundity
  • the relative viability of an individual over all loci (I will be examining from two to 32 loci influencing viability) is the product of the individual locus viability values
  • this multiplicative model is often assumed for viability loci
  • I assume there are two different types of loci, lethals and detrimentals, with different levels of dominance
  • Barrett & Charlesworth (1991) and D. Charlesworth (unpub. obs.) have actually examined the effects of self-fertilization on the genetic load in the presence of mutation and have reached general conclusions similar to those presented here
  • on the other hand, Lynch & Gabriel (1990) suggest that very small populations over a period of time may have a decline in fitness due to the fixation of new, detrimental mutants, leading to what they term a 'mutational meltdown'
  • however, R. Lande (unpub. obs.) has shown that mutational meltdown is of much less importance in influencing extinction than are other factors
  • I have assumed multiplicative fitness values over loci
  • if there are epistatic interactions such that the detrimental alleles reduce fitness more than the multiplicative model ..., then fitness may be lowered more than in the above simulations and the probability of extinction raised