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. 2002 Sep;162(1):459–471. doi: 10.1093/genetics/162.1.459

Joint effects of pleiotropic selection and stabilizing selection on the maintenance of quantitative genetic variation at mutation-selection balance.

Xu-Sheng Zhang 1, William G Hill 1
PMCID: PMC1462254  PMID: 12242254

Abstract

In quantitative genetics, there are two basic "conflicting" observations: abundant polygenic variation and strong stabilizing selection that should rapidly deplete that variation. This conflict, although having attracted much theoretical attention, still stands open. Two classes of model have been proposed: real stabilizing selection directly on the metric trait under study and apparent stabilizing selection caused solely by the deleterious pleiotropic side effects of mutations on fitness. Here these models are combined and the total stabilizing selection observed is assumed to derive simultaneously through these two different mechanisms. Mutations have effects on a metric trait and on fitness, and both effects vary continuously. The genetic variance (V(G)) and the observed strength of total stabilizing selection (V(s,t)) are analyzed with a rare-alleles model. Both kinds of selection reduce V(G) but their roles in depleting it are not independent: The magnitude of pleiotropic selection depends on real stabilizing selection and such dependence is subject to the shape of the distributions of mutational effects. The genetic variation maintained thus depends on the kurtosis as well as the variance of mutational effects: All else being equal, V(G) increases with increasing leptokurtosis of mutational effects on fitness, while for a given distribution of mutational effects on fitness, V(G) decreases with increasing leptokurtosis of mutational effects on the trait. The V(G) and V(s,t) are determined primarily by real stabilizing selection while pleiotropic effects, which can be large, have only a limited impact. This finding provides some promise that a high heritability can be explained under strong total stabilizing selection for what are regarded as typical values of mutation and selection parameters.

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Selected References

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  1. Barton N. H., Keightley P. D. Understanding quantitative genetic variation. Nat Rev Genet. 2002 Jan;3(1):11–21. doi: 10.1038/nrg700. [DOI] [PubMed] [Google Scholar]
  2. Barton N. H. Pleiotropic models of quantitative variation. Genetics. 1990 Mar;124(3):773–782. doi: 10.1093/genetics/124.3.773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barton N. H. The maintenance of polygenic variation through a balance between mutation and stabilizing selection. Genet Res. 1986 Jun;47(3):209–216. doi: 10.1017/s0016672300023156. [DOI] [PubMed] [Google Scholar]
  4. Barton N. H., Turelli M. Evolutionary quantitative genetics: how little do we know? Annu Rev Genet. 1989;23:337–370. doi: 10.1146/annurev.ge.23.120189.002005. [DOI] [PubMed] [Google Scholar]
  5. Bürger R., Gimelfarb A. Genetic variation maintained in multilocus models of additive quantitative traits under stabilizing selection. Genetics. 1999 Jun;152(2):807–820. doi: 10.1093/genetics/152.2.807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Caballero A., Keightley P. D. A pleiotropic nonadditive model of variation in quantitative traits. Genetics. 1994 Nov;138(3):883–900. doi: 10.1093/genetics/138.3.883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chavarrías D., López-Fanjul C., García-Dorado A. The rate of mutation and the homozygous and heterozygous mutational effects for competitive viability: a long-term experiment with Drosophila melanogaster. Genetics. 2001 Jun;158(2):681–693. doi: 10.1093/genetics/158.2.681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Davies E. K., Peters A. D., Keightley P. D. High frequency of cryptic deleterious mutations in Caenorhabditis elegans. Science. 1999 Sep 10;285(5434):1748–1751. doi: 10.1126/science.285.5434.1748. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Gillespie J. H. Pleiotropic overdominance and the maintenance of genetic variation in polygenic characters. Genetics. 1984 Jun;107(2):321–330. doi: 10.1093/genetics/107.2.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gillespie J. H., Turelli M. Genotype-environment interactions and the maintenance of polygenic variation. Genetics. 1989 Jan;121(1):129–138. doi: 10.1093/genetics/121.1.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gimelfarb A. How much genetic variation can be maintained by genotype-environment interactions? Genetics. 1990 Feb;124(2):443–447. doi: 10.1093/genetics/124.2.443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Imhof M., Schlotterer C. Fitness effects of advantageous mutations in evolving Escherichia coli populations. Proc Natl Acad Sci U S A. 2001 Jan 30;98(3):1113–1117. doi: 10.1073/pnas.98.3.1113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Keightley P. D., Caballero A. Genomic mutation rates for lifetime reproductive output and lifespan in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1997 Apr 15;94(8):3823–3827. doi: 10.1073/pnas.94.8.3823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Keightley P. D., Davies E. K., Peters A. D., Shaw R. G. Properties of ethylmethane sulfonate-induced mutations affecting life-history traits in Caenorhabditis elegans and inferences about bivariate distributions of mutation effects. Genetics. 2000 Sep;156(1):143–154. doi: 10.1093/genetics/156.1.143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. Kingsolver J. G., Hoekstra H. E., Hoekstra J. M., Berrigan D., Vignieri S. N., Hill C. E., Hoang A., Gibert P., Beerli P. The strength of phenotypic selection in natural populations. Am Nat. 2001 Mar;157(3):245–261. doi: 10.1086/319193. [DOI] [PubMed] [Google Scholar]
  20. Kondrashov A. S. Measuring spontaneous deleterious mutation process. Genetica. 1998;102-103(1-6):183–197. [PubMed] [Google Scholar]
  21. Kondrashov A. S., Turelli M. Deleterious mutations, apparent stabilizing selection and the maintenance of quantitative variation. Genetics. 1992 Oct;132(2):603–618. doi: 10.1093/genetics/132.2.603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kumar Sudhir, Subramanian Sankar. Mutation rates in mammalian genomes. Proc Natl Acad Sci U S A. 2002 Jan 15;99(2):803–808. doi: 10.1073/pnas.022629899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mackay T. F., Langley C. H. Molecular and phenotypic variation in the achaete-scute region of Drosophila melanogaster. Nature. 1990 Nov 1;348(6296):64–66. doi: 10.1038/348064a0. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Shaw R. G., Byers D. L., Darmo E. Spontaneous mutational effects on reproductive traits of arabidopsis thaliana. Genetics. 2000 May;155(1):369–378. doi: 10.1093/genetics/155.1.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Slatkin M. Frequency- and density-dependent selection on a quantitative character. Genetics. 1979 Nov;93(3):755–771. doi: 10.1093/genetics/93.3.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tanaka Y. A pleiotropic model of phenotypic evolution. Genetica. 1998;102-103(1-6):535–543. [PubMed] [Google Scholar]
  28. Tanaka Y. The Genetic Variance Maintained by Pleiotropic Mutation. Theor Popul Biol. 1996 Apr;49(2):211–231. doi: 10.1006/tpbi.1996.0012. [DOI] [PubMed] [Google Scholar]
  29. Turelli M. Effects of pleiotropy on predictions concerning mutation-selection balance for polygenic traits. Genetics. 1985 Sep;111(1):165–195. doi: 10.1093/genetics/111.1.165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Vassilieva L. L., Lynch M. The rate of spontaneous mutation for life-history traits in Caenorhabditis elegans. Genetics. 1999 Jan;151(1):119–129. doi: 10.1093/genetics/151.1.119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wloch D. M., Szafraniec K., Borts R. H., Korona R. Direct estimate of the mutation rate and the distribution of fitness effects in the yeast Saccharomyces cerevisiae. Genetics. 2001 Oct;159(2):441–452. doi: 10.1093/genetics/159.2.441. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Zhang Xu-Sheng, Wang Jinliang, Hill William G. Pleiotropic model of maintenance of quantitative genetic variation at mutation-selection balance. Genetics. 2002 May;161(1):419–433. doi: 10.1093/genetics/161.1.419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Zhivotovsky L. A., Gavrilets S. Quantitative variability and multilocus polymorphism under epistatic selection. Theor Popul Biol. 1992 Dec;42(3):254–283. doi: 10.1016/0040-5809(92)90015-l. [DOI] [PubMed] [Google Scholar]

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