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. 2003 Nov;165(3):1289–1305. doi: 10.1093/genetics/165.3.1289

Linkage disequilibrium patterns across a recombination gradient in African Drosophila melanogaster.

Peter Andolfatto 1, Jeffrey D Wall 1
PMCID: PMC1462864  PMID: 14668383

Abstract

Previous multilocus surveys of nucleotide polymorphism have documented a genome-wide excess of intralocus linkage disequilibrium (LD) in Drosophila melanogaster and D. simulans relative to expectations based on estimated mutation and recombination rates and observed levels of diversity. These studies examined patterns of variation from predominantly non-African populations that are thought to have recently expanded their ranges from central Africa. Here, we analyze polymorphism data from a Zimbabwean population of D. melanogaster, which is likely to be closer to the standard population model assumptions of a large population with constant size. Unlike previous studies, we find that levels of LD are roughly compatible with expectations based on estimated rates of crossing over. Further, a detailed examination of genes in different recombination environments suggests that markers near the telomere of the X chromosome show considerably less linkage disequilibrium than predicted by rates of crossing over, suggesting appreciable levels of exchange due to gene conversion. Assuming that these populations are near mutation-drift equilibrium, our results are most consistent with a model that posits heterogeneity in levels of exchange due to gene conversion across the X chromosome, with gene conversion being a minor determinant of LD levels in regions of high crossing over. Alternatively, if levels of exchange due to gene conversion are not negligible in regions of high crossing over, our results suggest a marked departure from mutation-drift equilibrium (i.e., toward an excess of LD) in this Zimbabwean population. Our results also have implications for the dynamics of weakly selected mutations in regions of reduced crossing over.

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Selected References

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  1. Andolfatto P. Contrasting patterns of X-linked and autosomal nucleotide variation in Drosophila melanogaster and Drosophila simulans. Mol Biol Evol. 2001 Mar;18(3):279–290. doi: 10.1093/oxfordjournals.molbev.a003804. [DOI] [PubMed] [Google Scholar]
  2. Andolfatto P., Kreitman M. Molecular variation at the In(2L)t proximal breakpoint site in natural populations of Drosophila melanogaster and D. simulans. Genetics. 2000 Apr;154(4):1681–1691. doi: 10.1093/genetics/154.4.1681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Andolfatto P., Nordborg M. The effect of gene conversion on intralocus associations. Genetics. 1998 Mar;148(3):1397–1399. doi: 10.1093/genetics/148.3.1397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Andolfatto P., Przeworski M. A genome-wide departure from the standard neutral model in natural populations of Drosophila. Genetics. 2000 Sep;156(1):257–268. doi: 10.1093/genetics/156.1.257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Andolfatto P., Przeworski M. Regions of lower crossing over harbor more rare variants in African populations of Drosophila melanogaster. Genetics. 2001 Jun;158(2):657–665. doi: 10.1093/genetics/158.2.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Andolfatto P., Wall J. D., Kreitman M. Unusual haplotype structure at the proximal breakpoint of In(2L)t in a natural population of Drosophila melanogaster. Genetics. 1999 Nov;153(3):1297–1311. doi: 10.1093/genetics/153.3.1297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Aquadro C. F., Bauer DuMont V., Reed F. A. Genome-wide variation in the human and fruitfly: a comparison. Curr Opin Genet Dev. 2001 Dec;11(6):627–634. doi: 10.1016/s0959-437x(00)00245-8. [DOI] [PubMed] [Google Scholar]
  8. Baines John F., Chen Ying, Das Aparup, Stephan Wolfgang. DNA sequence variation at a duplicated gene: excess of replacement polymorphism and extensive haplotype structure in the Drosophila melanogaster bicoid region. Mol Biol Evol. 2002 Jul;19(7):989–998. doi: 10.1093/oxfordjournals.molbev.a004179. [DOI] [PubMed] [Google Scholar]
  9. Begun D. J., Aquadro C. F. African and North American populations of Drosophila melanogaster are very different at the DNA level. Nature. 1993 Oct 7;365(6446):548–550. doi: 10.1038/365548a0. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Begun D. J., Aquadro C. F. Molecular variation at the vermilion locus in geographically diverse populations of Drosophila melanogaster and D. simulans. Genetics. 1995 Jul;140(3):1019–1032. doi: 10.1093/genetics/140.3.1019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Begun D. J., Whitley P. Reduced X-linked nucleotide polymorphism in Drosophila simulans. Proc Natl Acad Sci U S A. 2000 May 23;97(11):5960–5965. doi: 10.1073/pnas.97.11.5960. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Begun D. J., Whitley P., Todd B. L., Waldrip-Dail H. M., Clark A. G. Molecular population genetics of male accessory gland proteins in Drosophila. Genetics. 2000 Dec;156(4):1879–1888. doi: 10.1093/genetics/156.4.1879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Birdsell John A. Integrating genomics, bioinformatics, and classical genetics to study the effects of recombination on genome evolution. Mol Biol Evol. 2002 Jul;19(7):1181–1197. doi: 10.1093/oxfordjournals.molbev.a004176. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. 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]
  17. Charlesworth B. The effect of life-history and mode of inheritance on neutral genetic variability. Genet Res. 2001 Apr;77(2):153–166. doi: 10.1017/s0016672301004979. [DOI] [PubMed] [Google Scholar]
  18. Comeron Josep M., Kreitman Martin. Population, evolutionary and genomic consequences of interference selection. Genetics. 2002 May;161(1):389–410. doi: 10.1093/genetics/161.1.389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Eanes W. F., Kirchner M., Yoon J., Biermann C. H., Wang I. N., McCartney M. A., Verrelli B. C. Historical selection, amino acid polymorphism and lineage-specific divergence at the G6pd locus in Drosophila melanogaster and D. simulans. Genetics. 1996 Nov;144(3):1027–1041. doi: 10.1093/genetics/144.3.1027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Frisse L., Hudson R. R., Bartoszewicz A., Wall J. D., Donfack J., Di Rienzo A. Gene conversion and different population histories may explain the contrast between polymorphism and linkage disequilibrium levels. Am J Hum Genet. 2001 Aug 29;69(4):831–843. doi: 10.1086/323612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hamblin M. T., Veuille M. Population structure among African and derived populations of Drosophila simulans: evidence for ancient subdivision and recent admixture. Genetics. 1999 Sep;153(1):305–317. doi: 10.1093/genetics/153.1.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Hawley R. S., McKim K. S., Arbel T. Meiotic segregation in Drosophila melanogaster females: molecules, mechanisms, and myths. Annu Rev Genet. 1993;27:281–317. doi: 10.1146/annurev.ge.27.120193.001433. [DOI] [PubMed] [Google Scholar]
  24. Hey J., Wakeley J. A coalescent estimator of the population recombination rate. Genetics. 1997 Mar;145(3):833–846. doi: 10.1093/genetics/145.3.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hill W. G., Robertson A. The effect of linkage on limits to artificial selection. Genet Res. 1966 Dec;8(3):269–294. [PubMed] [Google Scholar]
  26. Hilliker A. J., Harauz G., Reaume A. G., Gray M., Clark S. H., Chovnick A. Meiotic gene conversion tract length distribution within the rosy locus of Drosophila melanogaster. Genetics. 1994 Aug;137(4):1019–1026. doi: 10.1093/genetics/137.4.1019. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Hudson R. R. Estimating the recombination parameter of a finite population model without selection. Genet Res. 1987 Dec;50(3):245–250. doi: 10.1017/s0016672300023776. [DOI] [PubMed] [Google Scholar]
  28. 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]
  29. Jensen Mark A., Charlesworth Brian, Kreitman Martin. Patterns of genetic variation at a chromosome 4 locus of Drosophila melanogaster and D. simulans. Genetics. 2002 Feb;160(2):493–507. doi: 10.1093/genetics/160.2.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. 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]
  31. Kauer M., Zangerl B., Dieringer D., Schlötterer C. Chromosomal patterns of microsatellite variability contrast sharply in African and non-African populations of Drosophila melanogaster. Genetics. 2002 Jan;160(1):247–256. doi: 10.1093/genetics/160.1.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Kliman R. M., Hey J. Reduced natural selection associated with low recombination in Drosophila melanogaster. Mol Biol Evol. 1993 Nov;10(6):1239–1258. doi: 10.1093/oxfordjournals.molbev.a040074. [DOI] [PubMed] [Google Scholar]
  33. Labate J. A., Biermann C. H., Eanes W. F. Nucleotide variation at the runt locus in Drosophila melanogaster and Drosophila simulans. Mol Biol Evol. 1999 Jun;16(6):724–731. doi: 10.1093/oxfordjournals.molbev.a026157. [DOI] [PubMed] [Google Scholar]
  34. Langley C. H., Lazzaro B. P., Phillips W., Heikkinen E., Braverman J. M. Linkage disequilibria and the site frequency spectra in the su(s) and su(w(a)) regions of the Drosophila melanogaster X chromosome. Genetics. 2000 Dec;156(4):1837–1852. doi: 10.1093/genetics/156.4.1837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Marais G., Mouchiroud D., Duret L. Does recombination improve selection on codon usage? Lessons from nematode and fly complete genomes. Proc Natl Acad Sci U S A. 2001 Apr 24;98(10):5688–5692. doi: 10.1073/pnas.091427698. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Marais Gabriel. Biased gene conversion: implications for genome and sex evolution. Trends Genet. 2003 Jun;19(6):330–338. doi: 10.1016/S0168-9525(03)00116-1. [DOI] [PubMed] [Google Scholar]
  37. Marais Gabriel, Piganeau Gwenaël. Hill-Robertson interference is a minor determinant of variations in codon bias across Drosophila melanogaster and Caenorhabditis elegans genomes. Mol Biol Evol. 2002 Sep;19(9):1399–1406. doi: 10.1093/oxfordjournals.molbev.a004203. [DOI] [PubMed] [Google Scholar]
  38. Maside Xulio, Bartolomé Carolina, Charlesworth Brian. S-element insertions are associated with the evolution of the Hsp70 genes in Drosophila melanogaster. Curr Biol. 2002 Oct 1;12(19):1686–1691. doi: 10.1016/s0960-9822(02)01181-8. [DOI] [PubMed] [Google Scholar]
  39. McVean G. A., Charlesworth B. The effects of Hill-Robertson interference between weakly selected mutations on patterns of molecular evolution and variation. Genetics. 2000 Jun;155(2):929–944. doi: 10.1093/genetics/155.2.929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. McVean G. A., Vieira J. Inferring parameters of mutation, selection and demography from patterns of synonymous site evolution in Drosophila. Genetics. 2001 Jan;157(1):245–257. doi: 10.1093/genetics/157.1.245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Odgers Wendy A., Aquadro Charles F., Coppin Christopher W., Healy Marion J., Oakeshott John G. Nucleotide polymorphism in the Est6 promoter, which is widespread in derived populations of Drosophila melanogaster, changes the level of Esterase 6 expressed in the male ejaculatory duct. Genetics. 2002 Oct;162(2):785–797. doi: 10.1093/genetics/162.2.785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Przeworski M., Wall J. D. Why is there so little intragenic linkage disequilibrium in humans? Genet Res. 2001 Apr;77(2):143–151. doi: 10.1017/s0016672301004967. [DOI] [PubMed] [Google Scholar]
  43. 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]
  44. Stephan W., Langley C. H. Evolutionary consequences of DNA mismatch inhibited repair opportunity. Genetics. 1992 Oct;132(2):567–574. doi: 10.1093/genetics/132.2.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Stephens J. C., Schneider J. A., Tanguay D. A., Choi J., Acharya T., Stanley S. E., Jiang R., Messer C. J., Chew A., Han J. H. Haplotype variation and linkage disequilibrium in 313 human genes. Science. 2001 Jul 12;293(5529):489–493. doi: 10.1126/science.1059431. [DOI] [PubMed] [Google Scholar]
  46. Szostak J. W., Orr-Weaver T. L., Rothstein R. J., Stahl F. W. The double-strand-break repair model for recombination. Cell. 1983 May;33(1):25–35. doi: 10.1016/0092-8674(83)90331-8. [DOI] [PubMed] [Google Scholar]
  47. Tachida H. Molecular evolution in a multisite nearly neutral mutation model. J Mol Evol. 2000 Jan;50(1):69–81. doi: 10.1007/s002399910008. [DOI] [PubMed] [Google Scholar]
  48. Tishkoff S. A., Dietzsch E., Speed W., Pakstis A. J., Kidd J. R., Cheung K., Bonné-Tamir B., Santachiara-Benerecetti A. S., Moral P., Krings M. Global patterns of linkage disequilibrium at the CD4 locus and modern human origins. Science. 1996 Mar 8;271(5254):1380–1387. doi: 10.1126/science.271.5254.1380. [DOI] [PubMed] [Google Scholar]
  49. Tsaur S. C., Ting C. T., Wu C. I. Positive selection driving the evolution of a gene of male reproduction, Acp26Aa, of Drosophila: II. Divergence versus polymorphism. Mol Biol Evol. 1998 Aug;15(8):1040–1046. doi: 10.1093/oxfordjournals.molbev.a026002. [DOI] [PubMed] [Google Scholar]
  50. Wall J. D. A comparison of estimators of the population recombination rate. Mol Biol Evol. 2000 Jan;17(1):156–163. doi: 10.1093/oxfordjournals.molbev.a026228. [DOI] [PubMed] [Google Scholar]
  51. Wall J. D. Insights from linked single nucleotide polymorphisms: what we can learn from linkage disequilibrium. Curr Opin Genet Dev. 2001 Dec;11(6):647–651. doi: 10.1016/s0959-437x(00)00248-3. [DOI] [PubMed] [Google Scholar]
  52. Wall Jeffrey D., Andolfatto Peter, Przeworski Molly. Testing models of selection and demography in Drosophila simulans. Genetics. 2002 Sep;162(1):203–216. doi: 10.1093/genetics/162.1.203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. 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]
  54. Wiuf C., Hein J. The coalescent with gene conversion. Genetics. 2000 May;155(1):451–462. doi: 10.1093/genetics/155.1.451. [DOI] [PMC free article] [PubMed] [Google Scholar]

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