Skip to main content
NCBI home page
Genetics logoLink to Genetics
. 2001 May;158(1):477–485. doi: 10.1093/genetics/158.1.477

Epistasis and the mutation load: a measurement-theoretical approach.

T F Hansen 1, G P Wagner 1
PMCID: PMC1461645  PMID: 11333254

Abstract

An approximate solution for the mean fitness in mutation-selection balance with arbitrary order of epistatic interaction is derived. The solution is based on the assumptions of coupling equilibrium and that the interaction effects are multilinear. We find that the effect of m-order epistatic interactions (i.e., interactions among groups of m loci) on the load is dependent on the total genomic mutation rate, U, to the mth power. Thus, higher-order gene interactions are potentially important if U is large and the interaction density among loci is not too low. The solution suggests that synergistic epistasis will decrease the mutation load and that variation in epistatic effects will elevate the load. Both of these results, however, are strictly true only if they refer to epistatic interaction strengths measured in the optimal genotype. If gene interactions are measured at mutation-selection equilibrium, only synergistic interactions among even numbers of genes will reduce the load. Odd-ordered synergistic interactions will then elevate the load. There is no systematic relationship between variation in epistasis and load at equilibrium. We argue that empirical estimates of gene interaction must pay attention to the genetic background in which the effects are measured and that it may be advantageous to refer to average interaction intensities as measured in mutation-selection equilibrium. We derive a simple criterion for the strength of epistasis that is necessary to overcome the twofold disadvantage of sex.

Full Text

The Full Text of this article is available as a PDF (222.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Clark A. G., Wang L. Epistasis in measured genotypes: Drosophila P-element insertions. Genetics. 1997 Sep;147(1):157–163. doi: 10.1093/genetics/147.1.157. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Elena S. F., Lenski R. E. Test of synergistic interactions among deleterious mutations in bacteria. Nature. 1997 Nov 27;390(6658):395–398. doi: 10.1038/37108. [DOI] [PubMed] [Google Scholar]
  3. Fenster C. B., Galloway L. F. Population differentiation in an annual legume: genetic architecture. Evolution. 2000 Aug;54(4):1157–1172. doi: 10.1111/j.0014-3820.2000.tb00551.x. [DOI] [PubMed] [Google Scholar]
  4. Gavrilets S., de Jong G. Pleiotropic models of polygenic variation, stabilizing selection, and epistasis. Genetics. 1993 Jun;134(2):609–625. doi: 10.1093/genetics/134.2.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hansen T. F., Price D. K. Age- and sex-distribution of the mutation load. Genetica. 1999;106(3):251–262. doi: 10.1023/a:1003988101586. [DOI] [PubMed] [Google Scholar]
  6. Kimura M., Maruyama T. The mutational load with epistatic gene interactions in fitness. Genetics. 1966 Dec;54(6):1337–1351. doi: 10.1093/genetics/54.6.1337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Kondrashov A. S. Deleterious mutations and the evolution of sexual reproduction. Nature. 1988 Dec 1;336(6198):435–440. doi: 10.1038/336435a0. [DOI] [PubMed] [Google Scholar]
  8. Kondrashov A. S. Deleterious mutations as an evolutionary factor. 1. The advantage of recombination. Genet Res. 1984 Oct;44(2):199–217. doi: 10.1017/s0016672300026392. [DOI] [PubMed] [Google Scholar]
  9. Kondrashov A. S. Muller's ratchet under epistatic selection. Genetics. 1994 Apr;136(4):1469–1473. doi: 10.1093/genetics/136.4.1469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kondrashov A. S. Selection against harmful mutations in large sexual and asexual populations. Genet Res. 1982 Dec;40(3):325–332. doi: 10.1017/s0016672300019194. [DOI] [PubMed] [Google Scholar]
  11. MULLER H. J. Our load of mutations. Am J Hum Genet. 1950 Jun;2(2):111–176. [PMC free article] [PubMed] [Google Scholar]
  12. Mukai T. The Genetic Structure of Natural Populations of DROSOPHILA MELANOGASTER. VII Synergistic Interaction of Spontaneous Mutant Polygenes Controlling Viability. Genetics. 1969 Mar;61(3):749–761. doi: 10.1093/genetics/61.3.749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Otto S. P., Feldman M. W. Deleterious mutations, variable epistatic interactions, and the evolution of recombination. Theor Popul Biol. 1997 Apr;51(2):134–147. doi: 10.1006/tpbi.1997.1301. [DOI] [PubMed] [Google Scholar]
  14. Polaczyk P. J., Gasperini R., Gibson G. Naturally occurring genetic variation affects Drosophila photoreceptor determination. Dev Genes Evol. 1998 Jan;207(7):462–470. doi: 10.1007/s004270050137. [DOI] [PubMed] [Google Scholar]
  15. Wagner G. P., Laubichler M. D., Bagheri-Chaichian H. Genetic measurement of theory of epistatic effects. Genetica. 1998;102-103(1-6):569–580. [PubMed] [Google Scholar]
  16. Whitlock M. C., Bourguet D. Factors affecting the genetic load in Drosophila: synergistic epistasis and correlations among fitness components. Evolution. 2000 Oct;54(5):1654–1660. doi: 10.1111/j.0014-3820.2000.tb00709.x. [DOI] [PubMed] [Google Scholar]
  17. de Visser J. A., Hoekstra R. F., van den Ende H. An experimental test for synergistic epistasis and its application in Chlamydomonas. Genetics. 1997 Mar;145(3):815–819. doi: 10.1093/genetics/145.3.815. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES