Skip to main content
Log in

The effect of recurrent mutation on the linkage disequilibrium under a selective sweep

  • Published:
Journal of Mathematical Biology Aims and scope Submit manuscript

Abstract

A selective sweep describes the reduction of diversity due to strong positive selection. If the mutation rate to a selectively beneficial allele is sufficiently high, Pennings and Hermisson (Mol Biol Evol 23(5):1076–1084, 2006a) have shown, that it becomes likely, that a selective sweep is caused by several individuals. Such an event is called a soft sweep and the complementary event of a single origin of the beneficial allele, the classical case, a hard sweep. We give analytical expressions for the linkage disequilibrium (LD) between two neutral loci linked to the selected locus, depending on the recurrent mutation to the beneficial allele, measured by D and \({\widehat{\sigma_D^2}}\), a quantity introduced by Ohta and Kimura (Genetics 63(1):229–238, 1969), and conclude that the LD-pattern of a soft sweep differs substantially from that of a hard sweep due to haplotype structure. The analytical results are compared with simulations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Barton NH, Etheridge AM, Sturm AK (2004) Coalescence in a random background. Ann Appl Probab 14(2): 754–785

    Article  MATH  MathSciNet  Google Scholar 

  • Durrett R, Schweinsberg J (2004) Approximating selective sweeps. Theo Pop Biol 66(2): 129–138

    Article  MATH  Google Scholar 

  • Etheridge AM, Pfaffelhuber P, Wakolbinger A (2006) An approximate sampling formula under genetic hitchhiking. Ann Appl Probab 16: 685–729

    Article  MATH  MathSciNet  Google Scholar 

  • Ewing G, Hermisson J (2010) Msms: a coalescent simulation program including recombination, demographic structure, and selection at a single locus. Bioinformatics 26(16): 2064–2065

    Article  Google Scholar 

  • Hermisson J, Pennings P (2005) Soft sweeps: molecular population genetics of adaptation from standing genetic variation. Genetics 169(4): 2335–2352

    Article  Google Scholar 

  • Hermisson J, Pfaffelhuber P (2008) The pattern of genetic hitchhiking under recurrent mutation. Elec J Prob 13(68): 2069–2106

    MATH  MathSciNet  Google Scholar 

  • Karasov T, Messer PW, Petrov DA (2010) Evidence that adaptation in Drosophila is not limited by mutation at single sites. PLoS Genet 6(6): e1000924

    Article  Google Scholar 

  • Kim Y, Nielsen R (2004) Linkage disequilibrium as a signature of selective sweeps. Genetics 167: 1513–1524

    Article  Google Scholar 

  • Kurtz TG (1971) Limit theorems for sequences of jump markov processes approximation ordinary differential processes. J Appl Prob 8: 344–356

    Article  MATH  MathSciNet  Google Scholar 

  • Maynard Smith J, Haigh J (1974) The hitch-hiking effect of a favorable gene. Gen Res 23: 23–35

    Article  Google Scholar 

  • McVean GA (2007) The structure of linkage disequilibrium around a selective sweep. Genetics 175: 1395–1406

    Article  Google Scholar 

  • Nair S, Nash D, Sudimack D, Jaidee A, Barends M, Uhlemann AC, Krishna S, Nosten F, Anderson TJ (2007) Recurrent gene amplification and soft selective sweeps during evolution of multidrug resistance in malaria parasites. Mol Biol Evol 24(2): 562–573

    Article  Google Scholar 

  • Ohta T, Kimura M (1969) Linkage disequilibrium at steady state determined by random genetic drift and recurrent mutation. Genetics 63(1): 229–238

    Google Scholar 

  • Pennings P, Hermisson J (2006a) Soft sweeps II—molecular population genetics of adaptation from recurrent mutation or migration. Mol Biol Evol 23(5): 1076–1084

    Article  Google Scholar 

  • Pennings P, Hermisson J (2006b) Soft sweeps III: the signature of positive selection from recurrent mutation. PLoS Genetics 2(12): 1998–2012

    Article  Google Scholar 

  • Pfaffelhuber P, Lehnert A, Stephan W (2008) Linkage disequilibrium under genetic hitchhiking in finite populations. Genetics 179: 527–537

    Article  Google Scholar 

  • Pfaffelhuber P, Studeny A (2007) Approximating genealogies for partially linked neutral loci under a selective sweep. J Math Biol 55: 299–330

    Article  MATH  MathSciNet  Google Scholar 

  • Pritchard JK, Pickrell JK, Coop G (2010) The genetics of human adaptation: hard sweeps, soft sweeps, and polygenic adaptation. Curr Biol 20(4): 208–215

    Article  Google Scholar 

  • Scheinfeldt LB, Biswas S, Madeoy J, Connelly CF, Schadt EE, Akey JM (2009) Population genomic analysis of ALMS1 in humans reveals a surprisingly complex evolutionary history. Mol Biol Evol 26(6): 1357–1367

    Article  Google Scholar 

  • Schlenke TA, Begun DJ (2005) Linkage disequilibrium and recent selection at three immunity receptor loci in Drosophila simulans. Genetics 169(4): 2013–2022

    Article  Google Scholar 

  • Song Y, Song J (2007) Analytic computation of the expectation of the linkage disequilibrium coefficient r 2. Theo Pop Biol 71: 49–60

    Article  MATH  Google Scholar 

  • Stephan W, Song YS, Langley CH (2006) The hitchhiking effect on linkage disequilibrium between linked neutral loci. Genetics 172(4): 2647–2663

    Article  Google Scholar 

  • Tishkoff SA, Reed FA, Ranciaro A, Voight BF, Babbitt CC, Silverman JS, Powell K, Mortensen HM, Hirbo JB, Osman M, Ibrahim M, Omar SA, Lema G, Nyambo TB, Ghori J, Bumpstead S, Pritchard JK, Wray GA, Deloukas P (2007) Convergent adaptation of human lactase persistence in Africa and Europe. Nat Genet 39: 31–40

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Cornelia Pokalyuk.

Electronic Supplementary Material

The Below is the Electronic Supplementary Material.

ESM 1 (NB 41 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pokalyuk, C. The effect of recurrent mutation on the linkage disequilibrium under a selective sweep. J. Math. Biol. 64, 291–317 (2012). https://doi.org/10.1007/s00285-011-0411-y

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00285-011-0411-y

Keywords

Mathematics Subject Classification (2000)

Navigation