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. 2002 Jun;161(2):897–904. doi: 10.1093/genetics/161.2.897

Nonequivalent Loci and the distribution of mutant effects.

J J Welch 1, D Waxman 1
PMCID: PMC1462143  PMID: 12072483

Abstract

It has been observed repeatedly that the distribution of new mutations of a quantitative trait has a kurtosis (a statistical measure of the distribution's shape) that is systematically larger than that of a normal distribution. Here we suggest that rather than being a property of individual loci that control the trait, the enhanced kurtosis is highly likely to be an emergent property that arises directly from the loci being mutationally nonequivalent. We present a method of incorporating nonequivalent loci into quantitative genetic modeling and give an approximate relation between the kurtosis of the mutant distribution and the degree of mutational nonequivalence of loci. We go on to ask whether incorporating the experimentally observed kurtosis through nonequivalent loci, rather than at locus level, affects any biologically important conclusions of quantitative genetic modeling. Concentrating on the maintenance of quantitative genetic variation by mutation-selection balance, we conclude that typically nonequivalent loci yield a genetic variance that is of order 10% smaller than that obtained from the previous approaches. For large populations, when the kurtosis is large, the genetic variance may be <50% of the result of equivalent loci, with Gaussian distributions of mutant effects.

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Selected References

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  1. Bost B., Dillmann C., de Vienne D. Fluxes and metabolic pools as model traits for quantitative genetics. I. The L-shaped distribution of gene effects. Genetics. 1999 Dec;153(4):2001–2012. doi: 10.1093/genetics/153.4.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bost B., Dillmann C., de Vienne D. Fluxes and metabolic pools as model traits for quantitative genetics. I. The L-shaped distribution of gene effects. Genetics. 1999 Dec;153(4):2001–2012. doi: 10.1093/genetics/153.4.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bost B., de Vienne D., Hospital F., Moreau L., Dillmann C. Genetic and nongenetic bases for the L-shaped distribution of quantitative trait loci effects. Genetics. 2001 Apr;157(4):1773–1787. doi: 10.1093/genetics/157.4.1773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bürger R. Evolution of genetic variability and the advantage of sex and recombination in changing environments. Genetics. 1999 Oct;153(2):1055–1069. doi: 10.1093/genetics/153.2.1055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bürger R., Lande R. On the distribution of the mean and variance of a quantitative trait under mutation-selection-drift balance. Genetics. 1994 Nov;138(3):901–912. doi: 10.1093/genetics/138.3.901. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. García-Dorado A., López-Fanjul C., Caballero A. Properties of spontaneous mutations affecting quantitative traits. Genet Res. 1999 Dec;74(3):341–350. doi: 10.1017/s0016672399004206. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Houle D., Morikawa B., Lynch M. Comparing mutational variabilities. Genetics. 1996 Jul;143(3):1467–1483. doi: 10.1093/genetics/143.3.1467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Keightley P. D., Hill W. G. Quantitative genetic variability maintained by mutation-stabilizing selection balance in finite populations. Genet Res. 1988 Aug;52(1):33–43. doi: 10.1017/s0016672300027282. [DOI] [PubMed] [Google Scholar]
  10. Keightley P. D., Hill W. G. Quantitative genetic variability maintained by mutation-stabilizing selection balance: sampling variation and response to subsequent directional selection. Genet Res. 1989 Aug;54(1):45–57. doi: 10.1017/s0016672300028366. [DOI] [PubMed] [Google Scholar]
  11. Keightley P. D., Ohnishi O. EMS-induced polygenic mutation rates for nine quantitative characters in Drosophila melanogaster. Genetics. 1998 Feb;148(2):753–766. doi: 10.1093/genetics/148.2.753. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kimura M. A stochastic model concerning the maintenance of genetic variability in quantitative characters. Proc Natl Acad Sci U S A. 1965 Sep;54(3):731–736. doi: 10.1073/pnas.54.3.731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lande R. The maintenance of genetic variability by mutation in a polygenic character with linked loci. Genet Res. 1975 Dec;26(3):221–235. doi: 10.1017/s0016672300016037. [DOI] [PubMed] [Google Scholar]
  14. Lyman R. F., Lawrence F., Nuzhdin S. V., Mackay T. F. Effects of single P-element insertions on bristle number and viability in Drosophila melanogaster. Genetics. 1996 May;143(1):277–292. doi: 10.1093/genetics/143.1.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lynch M. Design and analysis of experiments on random drift and inbreeding depression. Genetics. 1988 Nov;120(3):791–807. doi: 10.1093/genetics/120.3.791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mackay T. F., Fry J. D., Lyman R. F., Nuzhdin S. V. Polygenic mutation in Drosophila melanogaster: estimates from response to selection of inbred strains. Genetics. 1994 Mar;136(3):937–951. doi: 10.1093/genetics/136.3.937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mackay T. F., Lyman R. F., Jackson M. S. Effects of P element insertions on quantitative traits in Drosophila melanogaster. Genetics. 1992 Feb;130(2):315–332. doi: 10.1093/genetics/130.2.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nuzhdin S. V., Fry J. D., Mackay T. F. Polygenic mutation in Drosophila melanogaster: the causal relationship of bristle number to fitness. Genetics. 1995 Feb;139(2):861–872. doi: 10.1093/genetics/139.2.861. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Turelli M. Heritable genetic variation via mutation-selection balance: Lerch's zeta meets the abdominal bristle. Theor Popul Biol. 1984 Apr;25(2):138–193. doi: 10.1016/0040-5809(84)90017-0. [DOI] [PubMed] [Google Scholar]
  20. Waxman D., Peck J. R. Sex and adaptation in a changing environment. Genetics. 1999 Oct;153(2):1041–1053. doi: 10.1093/genetics/153.2.1041. [DOI] [PMC free article] [PubMed] [Google Scholar]

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