Detecting a local signature of genetic hitchhiking along a recombining chromosome (original) (raw)

Abstract

The theory of genetic hitchhiking predicts that the level of genetic variation is greatly reduced at the site of strong directional selection and increases as the recombinational distance from the site of selection increases. This characteristic pattern can be used to detect recent directional selection on the basis of DNA polymorphism data. However, the large variance of nucleotide diversity in samples of moderate size imposes difficulties in detecting such patterns. We investigated the patterns of genetic variation along a recombining chromosome by constructing ancestral recombination graphs that are modified to incorporate the effect of genetic hitchhiking. A statistical method is proposed to test the significance of a local reduction of variation and a skew of the frequency spectrum caused by a hitchhiking event. This method also allows us to estimate the strength and the location of directional selection from DNA sequence data.

Full Text

The Full Text of this article is available as a PDF (445.7 KB).

Selected References

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

  1. Barton N. H. Genetic hitchhiking. Philos Trans R Soc Lond B Biol Sci. 2000 Nov 29;355(1403):1553–1562. doi: 10.1098/rstb.2000.0716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Begun D. J., Aquadro C. F. Levels of naturally occurring DNA polymorphism correlate with recombination rates in D. melanogaster. Nature. 1992 Apr 9;356(6369):519–520. doi: 10.1038/356519a0. [DOI] [PubMed] [Google Scholar]
  3. Braverman J. M., Hudson R. R., Kaplan N. L., Langley C. H., Stephan W. The hitchhiking effect on the site frequency spectrum of DNA polymorphisms. Genetics. 1995 Jun;140(2):783–796. doi: 10.1093/genetics/140.2.783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bénassi V., Depaulis F., Meghlaoui G. K., Veuille M. Partial sweeping of variation at the Fbp2 locus in a west African population of Drosophila melanogaster. Mol Biol Evol. 1999 Mar;16(3):347–353. doi: 10.1093/oxfordjournals.molbev.a026115. [DOI] [PubMed] [Google Scholar]
  5. Charlesworth B., Morgan M. T., Charlesworth D. The effect of deleterious mutations on neutral molecular variation. Genetics. 1993 Aug;134(4):1289–1303. doi: 10.1093/genetics/134.4.1289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Fu Y. X. Statistical tests of neutrality of mutations against population growth, hitchhiking and background selection. Genetics. 1997 Oct;147(2):915–925. doi: 10.1093/genetics/147.2.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fullerton S. M., Clark A. G., Weiss K. M., Nickerson D. A., Taylor S. L., Stengârd J. H., Salomaa V., Vartiainen E., Perola M., Boerwinkle E. Apolipoprotein E variation at the sequence haplotype level: implications for the origin and maintenance of a major human polymorphism. Am J Hum Genet. 2000 Sep 13;67(4):881–900. doi: 10.1086/303070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Galtier N., Depaulis F., Barton N. H. Detecting bottlenecks and selective sweeps from DNA sequence polymorphism. Genetics. 2000 Jun;155(2):981–987. doi: 10.1093/genetics/155.2.981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Hudson R. R. Properties of a neutral allele model with intragenic recombination. Theor Popul Biol. 1983 Apr;23(2):183–201. doi: 10.1016/0040-5809(83)90013-8. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Kim Y., Stephan W. Joint effects of genetic hitchhiking and background selection on neutral variation. Genetics. 2000 Jul;155(3):1415–1427. doi: 10.1093/genetics/155.3.1415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kimura M. Theoretical foundation of population genetics at the molecular level. Theor Popul Biol. 1971 Jun;2(2):174–208. doi: 10.1016/0040-5809(71)90014-1. [DOI] [PubMed] [Google Scholar]
  15. Nachman M. W., Crowell S. L. Contrasting evolutionary histories of two introns of the duchenne muscular dystrophy gene, Dmd, in humans. Genetics. 2000 Aug;155(4):1855–1864. doi: 10.1093/genetics/155.4.1855. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Nurminsky D., Aguiar D. D., Bustamante C. D., Hartl D. L. Chromosomal effects of rapid gene evolution in Drosophila melanogaster. Science. 2001 Jan 5;291(5501):128–130. doi: 10.1126/science.291.5501.128. [DOI] [PubMed] [Google Scholar]
  17. Rannala B., Slatkin M. Methods for multipoint disease mapping using linkage disequilibrium. Genet Epidemiol. 2000;19 (Suppl 1):S71–S77. doi: 10.1002/1098-2272(2000)19:1+<::AID-GEPI11>3.0.CO;2-D. [DOI] [PubMed] [Google Scholar]
  18. Smith J. M., Haigh J. The hitch-hiking effect of a favourable gene. Genet Res. 1974 Feb;23(1):23–35. [PubMed] [Google Scholar]
  19. 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]
  20. Stephan W., Xing L., Kirby D. A., Braverman J. M. A test of the background selection hypothesis based on nucleotide data from Drosophila ananassae. Proc Natl Acad Sci U S A. 1998 May 12;95(10):5649–5654. doi: 10.1073/pnas.95.10.5649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. 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]
  23. Wang R. L., Stec A., Hey J., Lukens L., Doebley J. The limits of selection during maize domestication. Nature. 1999 Mar 18;398(6724):236–239. doi: 10.1038/18435. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Wiuf C., Hein J. The ancestry of a sample of sequences subject to recombination. Genetics. 1999 Mar;151(3):1217–1228. doi: 10.1093/genetics/151.3.1217. [DOI] [PMC free article] [PubMed] [Google Scholar]