, 102:229 | Cite as

Inferences on genome-wide deleterious mutation rates in inbred populations of Drosophila and mice

  • Armando Caballero
  • Peter D. Keightley


A theoretical analysis was carried out on the mutation load observed in long-maintained inbred lines from two experiments with Drosophila and mice. The rate of decline in fitness and its sampling distribution were predicted for both experiments using Monte Carlo simulation with a range of mutational parameters and models. The predicted rates of change in fitness were compared to the empirical observed rates, which were close to zero. The classical hypothesis of many deleterious mutations (about one event per genome per generation) of small effect (1–2%) resulting in a mutation pressure for fitness of about 1% per generation is incompatible with the data. Recent estimates suggesting an overall mutation pressure for fitness traits of about 0.1% are, however, compatible with the observed load.

evolution fertility natural selection population genetics viability 


  1. Barton, N.H. & M. Turelli, 1989. Evolutionary Quantitative Genetics: How little do we know? Ann. Rev. Genet. 23: 337-370.PubMedGoogle Scholar
  2. Caballero, A. & P.D. Keightley, 1994. A pleiotropic nonadditive model of variation in quantitative traits. Genetics 138: 883-900.PubMedGoogle Scholar
  3. Caballero, A., P.D. Keightley & W.G. Hill, 1991. Strategies for increasing fixation probabilities of recessive mutations. Genet. Res. 58: 129-138.Google Scholar
  4. Caballero, A., P.D. Keightley & W.G. Hill, 1995. Accumulation of mutations affecting body weight in inbred mouse lines. Genet. Res. 65: 145-149.PubMedGoogle Scholar
  5. Caballero, A. & E. Santiago, 1995. Response to selection from new mutation and effective size of partially inbred populations. I. Theoretical Results. Genet. Res. 66: 213-225.Google Scholar
  6. Charlesworth, B., 1990. Mutation-selection balance and the evolutionary advantage of sex and recombination. Genet. Res. 55: 199-221.PubMedCrossRefGoogle Scholar
  7. Charlesworth, B., M.T. Morgan & D. Charlesworth, 1993. Mutation accumulation in finite outbreeding and inbreeding populations. Genet. Res. 61: 39-56.Google Scholar
  8. Charlesworth, B., D. Charlesworth & M.T. Morgan, 1990. Genetic loads and estimates of mutation rates in highly inbred plant populations. Nature 347: 380-382.CrossRefGoogle Scholar
  9. Charlesworth, D., E.E. Lyons & L.B. Litchfield, 1994. Inbreeding depression in two highly inbreeding populations of Leavenworthia. Proc. R. Soc. Lond. B 258: 209-214.Google Scholar
  10. Charlesworth, B. & K.A. Hughes, 1998. The maintenance of genetic variation in life history traits. In Evolutionary Genetics From Molecules toMorphology, edited by R.S. Singh & C.B. Krimbas. Cambridge University Press. (In press).Google Scholar
  11. Crow, J.F., 1993. Mutation, mean fitness and genetic load. Oxford Surv. Evol. Biol. 9: 3-42.Google Scholar
  12. Crow, J.F. & M. Kimura, 1970. An Introduction to Population Genetics Theory. Harper & Row, N.Y, USA.Google Scholar
  13. Deng, H.W. & M. Lynch, 1996. Estimation of deleterious-mutation parameters in natural populations. Genetics 144: 349-360.PubMedGoogle Scholar
  14. Fernández, J. & C. López-Fanjul, 1996. Spontaneous mutational variances and covariances for fitness-related traits in Drosophila melanogaster. Genetics 143: 829-837.PubMedGoogle Scholar
  15. Fernández, J. & C. López-Fanjul, 1997. Spontaneous mutational genotype-environmental interaction for fitness-related traits in Drosophila melanogaster. Evolution 51: 856-864.CrossRefGoogle Scholar
  16. García, N., C. López-Fanjul & A. García-Dorado, 1994. The genetics of viability in Drosophila melanogaster: effects of inbreeding and artificial selection. Evolution 48: 1277-1285.CrossRefGoogle Scholar
  17. García-Dorado, A., 1997. The rate and effects distribution of viability mutation in Drosophila: minimum distance estimation. Evolution 51: 1130-1139.CrossRefGoogle Scholar
  18. Johnston, M.O. & D.J. Schoen, 1995. Mutation rates and dominance levels of genes affecting total fitness in two angiosperm species. Science 267: 226-229.PubMedGoogle Scholar
  19. Keightley, P.D., 1994. The distribution of mutation effects on viability in Drosophila melanogaster. Genetics 138: 1315-1322.PubMedGoogle Scholar
  20. Keightley, P.D., 1996. Nature of deleterious mutation load in Drosophila. Genetics 144: 1993-1999.PubMedGoogle Scholar
  21. Keightley, P.D. & A. Caballero, 1997. Genomic mutation rates for lifetime reproductive output and life span in Caenorhabditis elegans. Proc. Natl. Acad. Sci. U.S.A. 94: 3823-3827.PubMedCrossRefGoogle Scholar
  22. Keightley, P.D. & W.G. Hill, 1992. Quantitative genetic variation in body size of mice from new mutation. Genetics 131: 693-700.PubMedGoogle Scholar
  23. Kibota, T.T. & M. Lynch, 1996. Estimate of the genomic mutation rate deleterious to overall fitness in E. coli. Nature 381: 694-696.PubMedCrossRefGoogle Scholar
  24. Kimura, M., 1962. On the probability of fixation of mutant genes in a population. Genetics 47: 713-719.PubMedGoogle Scholar
  25. Kondrashov, A.S., 1988. Deleterious mutations and the evolution of sexual reproduction. Nature 336: 435-440.PubMedCrossRefGoogle Scholar
  26. Kondrashov, A.S., 1995. Contamination of the genome by very slightly deleterious mutations: why have we not died 100 times over? J. Theor. Biol. 175: 583-594.PubMedCrossRefGoogle Scholar
  27. Kondrashov, A.S. & D. Houle, 1994. Genotype-environment interactions and the estimation of the genomic mutation rate in Drosophila melanogaster. Proc. R. Soc. Lond. B 258: 221-227.Google Scholar
  28. Lande, R., 1994. Risk of population extinction from fixation of new deleterious mutations. Evolution 48: 1460-1469.CrossRefGoogle Scholar
  29. Lande, R., 1995. Mutation and conservation. Conservation Biology 9: 782-791.Google Scholar
  30. López-Fanjul, C. & A. Villaverde, 1989. Inbreeding increases genetic variance for viability in Drosophila melanogaster. Evolution 43: 1800-1804.CrossRefGoogle Scholar
  31. Lynch, M., J. Conery & R. Burger, 1995. Mutation accumulation and extinction of small populations. Am. Nat. 146: 489-518.CrossRefGoogle Scholar
  32. Mackay, T.F.C., 1985. A quantitative genetic analysis of fitness and its componenets in Drosophila melanogaster. Genet. Res. 47: 59-70.Google Scholar
  33. Merchante, M., A. Caballero & C. LópezFanjul, 1995. Response to selection from new mutation and effective size of partially inbred populations. II. Experiments with Drosophila melanogaster. Genet. Res. 66: 227-240.PubMedGoogle Scholar
  34. Mukai, T., 1964. The genetic structure of natural populations of Drosophila melanogaster. I. Spontaneous mutation rate of polygenes controlling viability. Genetics 50: 1-19.PubMedGoogle Scholar
  35. Mukai, T., 1969. The genetic structure of natural populations of Drosophila melanogaster. VII. Synergistic interaction of spontaneous mutant polygenes controlling viability. Genetics 61: 749-761.PubMedGoogle Scholar
  36. Mukai, T., S.I. Chigusa, L.E. Mettler & J.F. Crow, 1972. Mutation rate and dominance of genes affecting viability in Drosophila melanogaster. Genetics 72: 333-355.Google Scholar
  37. Ohnishi, O., 1977. Spontaneous and ethyl methanesulfonate-induced mutations controlling viability in Drosophila melanogaster. II. Homozygous effect of polygenic mutations. Genetics 87: 529-545.PubMedGoogle Scholar
  38. Peck, J.R. & A. Eyre-Walker, 1997. The muddle about mutations. Nature 387: 135-136.PubMedCrossRefGoogle Scholar
  39. Sved, J.A., 1975. Fitness of third chromosome homozygotes in Drosophila melanogaster. Genet. Res. 25: 197-200.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Armando Caballero
    • 1
  • Peter D. Keightley
    • 1
  1. 1.Dep. Bioquímica, Genética e Inmunología, Facultad de CienciasUniversidad de VigoVigoSpain (Phone

Personalised recommendations