Skip to main content
PMC home page
Genetics logoLink to Genetics
. 2004 Jul;167(3):1513–1524. doi: 10.1534/genetics.103.025387

Linkage disequilibrium as a signature of selective sweeps.

Yuseob Kim 1, Rasmus Nielsen 1
PMCID: PMC1470945  PMID: 15280259

Abstract

The hitchhiking effect of a beneficial mutation, or a selective sweep, generates a unique distribution of allele frequencies and spatial distribution of polymorphic sites. A composite-likelihood test was previously designed to detect these signatures of a selective sweep, solely on the basis of the spatial distribution and marginal allele frequencies of polymorphisms. As an excess of linkage disequilibrium (LD) is also known to be a strong signature of a selective sweep, we investigate how much statistical power is increased by the inclusion of information regarding LD. The expected pattern of LD is predicted by a genealogical approach. Both theory and simulation suggest that strong LD is generated in narrow regions at both sides of the location of beneficial mutation. However, a lack of LD is expected across the two sides. We explore various ways to detect this signature of selective sweeps by statistical tests. A new composite-likelihood method is proposed to incorporate information regarding LD. This method enables us to detect selective sweeps and estimate the parameters of the selection model better than the previous composite-likelihood method that does not take LD into account. However, the improvement made by including LD is rather small, suggesting that most of the relevant information regarding selective sweeps is captured by the spatial distribution and marginal allele frequencies of polymorphisms.

Full Text

The Full Text of this article is available as a PDF (165.8 KB).

Selected References

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

  1. Aguadé M., Miyashita N., Langley C. H. Polymorphism and divergence in the Mst26A male accessory gland gene region in Drosophila. Genetics. 1992 Nov;132(3):755–770. doi: 10.1093/genetics/132.3.755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bustamante Carlos D., Nielsen Rasmus, Sawyer Stanley A., Olsen Kenneth M., Purugganan Michael D., Hartl Daniel L. The cost of inbreeding in Arabidopsis. Nature. 2002 Apr 4;416(6880):531–534. doi: 10.1038/416531a. [DOI] [PubMed] [Google Scholar]
  3. Depaulis F., Veuille M. Neutrality tests based on the distribution of haplotypes under an infinite-site model. Mol Biol Evol. 1998 Dec;15(12):1788–1790. doi: 10.1093/oxfordjournals.molbev.a025905. [DOI] [PubMed] [Google Scholar]
  4. Fay J. C., Wu C. I. Hitchhiking under positive Darwinian selection. Genetics. 2000 Jul;155(3):1405–1413. doi: 10.1093/genetics/155.3.1405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fay J. C., Wyckoff G. J., Wu C. I. Positive and negative selection on the human genome. Genetics. 2001 Jul;158(3):1227–1234. doi: 10.1093/genetics/158.3.1227. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Harr Bettina, Kauer Max, Schlötterer Christian. Hitchhiking mapping: a population-based fine-mapping strategy for adaptive mutations in Drosophilamelanogaster. Proc Natl Acad Sci U S A. 2002 Sep 26;99(20):12949–12954. doi: 10.1073/pnas.202336899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hudson R. R., Kreitman M., Aguadé M. A test of neutral molecular evolution based on nucleotide data. Genetics. 1987 May;116(1):153–159. doi: 10.1093/genetics/116.1.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hudson R. R. Two-locus sampling distributions and their application. Genetics. 2001 Dec;159(4):1805–1817. doi: 10.1093/genetics/159.4.1805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kaplan N. L., Hudson R. R., Langley C. H. The "hitchhiking effect" revisited. Genetics. 1989 Dec;123(4):887–899. doi: 10.1093/genetics/123.4.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kelly J. K. A test of neutrality based on interlocus associations. Genetics. 1997 Jul;146(3):1197–1206. doi: 10.1093/genetics/146.3.1197. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kim Yuseob, Stephan Wolfgang. Detecting a local signature of genetic hitchhiking along a recombining chromosome. Genetics. 2002 Feb;160(2):765–777. doi: 10.1093/genetics/160.2.765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. McVean Gilean A. T. A genealogical interpretation of linkage disequilibrium. Genetics. 2002 Oct;162(2):987–991. doi: 10.1093/genetics/162.2.987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nielsen R. Estimation of population parameters and recombination rates from single nucleotide polymorphisms. Genetics. 2000 Feb;154(2):931–942. doi: 10.1093/genetics/154.2.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nielsen Rasmus, Yang Ziheng. Estimating the distribution of selection coefficients from phylogenetic data with applications to mitochondrial and viral DNA. Mol Biol Evol. 2003 May 30;20(8):1231–1239. doi: 10.1093/molbev/msg147. [DOI] [PubMed] [Google Scholar]
  15. Nordborg Magnus, Tavaré Simon. Linkage disequilibrium: what history has to tell us. Trends Genet. 2002 Feb;18(2):83–90. doi: 10.1016/s0168-9525(02)02557-x. [DOI] [PubMed] [Google Scholar]
  16. Parsch J., Meiklejohn C. D., Hartl D. L. Patterns of DNA sequence variation suggest the recent action of positive selection in the janus-ocnus region of Drosophila simulans. Genetics. 2001 Oct;159(2):647–657. doi: 10.1093/genetics/159.2.647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Piganeau Gwenaël, Eyre-Walker Adam. Estimating the distribution of fitness effects from DNA sequence data: implications for the molecular clock. Proc Natl Acad Sci U S A. 2003 Aug 18;100(18):10335–10340. doi: 10.1073/pnas.1833064100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Przeworski Molly. Estimating the time since the fixation of a beneficial allele. Genetics. 2003 Aug;164(4):1667–1676. doi: 10.1093/genetics/164.4.1667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Przeworski Molly. The signature of positive selection at randomly chosen loci. Genetics. 2002 Mar;160(3):1179–1189. doi: 10.1093/genetics/160.3.1179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Quesada Humberto, Ramírez Ursula E. M., Rozas Julio, Aguadé Montserrat. Large-scale adaptive hitchhiking upon high recombination in Drosophila simulans. Genetics. 2003 Oct;165(2):895–900. doi: 10.1093/genetics/165.2.895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sabeti Pardis C., Reich David E., Higgins John M., Levine Haninah Z. P., Richter Daniel J., Schaffner Stephen F., Gabriel Stacey B., Platko Jill V., Patterson Nick J., McDonald Gavin J. Detecting recent positive selection in the human genome from haplotype structure. Nature. 2002 Oct 9;419(6909):832–837. doi: 10.1038/nature01140. [DOI] [PubMed] [Google Scholar]
  22. Schlenke Todd A., Begun David J. Strong selective sweep associated with a transposon insertion in Drosophila simulans. Proc Natl Acad Sci U S A. 2004 Jan 26;101(6):1626–1631. doi: 10.1073/pnas.0303793101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Smith J. M., Haigh J. The hitch-hiking effect of a favourable gene. Genet Res. 1974 Feb;23(1):23–35. [PubMed] [Google Scholar]
  24. Smith J. M. What use is sex? J Theor Biol. 1971 Feb;30(2):319–335. doi: 10.1016/0022-5193(71)90058-0. [DOI] [PubMed] [Google Scholar]
  25. Stephan W. An improved method for estimating the rate of fixation of favorable mutations based on DNA polymorphism data. Mol Biol Evol. 1995 Sep;12(5):959–962. doi: 10.1093/oxfordjournals.molbev.a040274. [DOI] [PubMed] [Google Scholar]
  26. Tajima F. Evolutionary relationship of DNA sequences in finite populations. Genetics. 1983 Oct;105(2):437–460. doi: 10.1093/genetics/105.2.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Tajima F. Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics. 1989 Nov;123(3):585–595. doi: 10.1093/genetics/123.3.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Vigouroux Y., McMullen M., Hittinger C. T., Houchins K., Schulz L., Kresovich S., Matsuoka Y., Doebley J. Identifying genes of agronomic importance in maize by screening microsatellites for evidence of selection during domestication. Proc Natl Acad Sci U S A. 2002 Jul 8;99(15):9650–9655. doi: 10.1073/pnas.112324299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Watterson G. A. On the number of segregating sites in genetical models without recombination. Theor Popul Biol. 1975 Apr;7(2):256–276. doi: 10.1016/0040-5809(75)90020-9. [DOI] [PubMed] [Google Scholar]
  30. Wootton John C., Feng Xiaorong, Ferdig Michael T., Cooper Roland A., Mu Jianbing, Baruch Dror I., Magill Alan J., Su Xin-Zhuan. Genetic diversity and chloroquine selective sweeps in Plasmodium falciparum. Nature. 2002 Jul 18;418(6895):320–323. doi: 10.1038/nature00813. [DOI] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES