Abstract
A stochastic model for the genealogy of a sample of recombining sequences containing one or more sites subject to selection in a subdivided population is described. Selection is incorporated by dividing the population into allelic classes and then conditioning on the past sizes of these classes. The past allele frequencies at the selected sites are thus treated as parameters rather than as random variables. The purpose of the model is not to investigate the dynamics of selection, but to investigate effects of linkage to the selected sites on the genealogy of the surrounding chromosomal region. This approach is useful for modeling strong selection, when it is natural to parameterize the past allele frequencies at the selected sites. Several models of strong balancing selection are used as examples, and the effects on the pattern of neutral polymorphism in the chromosomal region are discussed. We focus in particular on the statistical power to detect balancing selection when it is present.
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- 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]
- Barton Nick H., Navarro Arcadio. Extending the coalescent to multilocus systems: the case of balancing selection. Genet Res. 2002 Apr;79(2):129–139. doi: 10.1017/s0016672301005493. [DOI] [PubMed] [Google Scholar]
- 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]
- Campbell R. B. The coalescent time in the presence of background fertility selection. Theor Popul Biol. 1999 Jun;55(3):260–269. doi: 10.1006/tpbi.1998.1402. [DOI] [PubMed] [Google Scholar]
- Fearnhead P. Perfect simulation from population genetic models with selection. Theor Popul Biol. 2001 Jun;59(4):263–279. doi: 10.1006/tpbi.2001.1514. [DOI] [PubMed] [Google Scholar]
- Hey J. A multi-dimensional coalescent process applied to multi-allelic selection models and migration models. Theor Popul Biol. 1991 Feb;39(1):30–48. doi: 10.1016/0040-5809(91)90039-i. [DOI] [PubMed] [Google Scholar]
- Hudson R. R., Bailey K., Skarecky D., Kwiatowski J., Ayala F. J. Evidence for positive selection in the superoxide dismutase (Sod) region of Drosophila melanogaster. Genetics. 1994 Apr;136(4):1329–1340. doi: 10.1093/genetics/136.4.1329. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hudson R. R., Kaplan N. L. Deleterious background selection with recombination. Genetics. 1995 Dec;141(4):1605–1617. doi: 10.1093/genetics/141.4.1605. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hudson R. R., Kaplan N. L. The coalescent process in models with selection and recombination. Genetics. 1988 Nov;120(3):831–840. doi: 10.1093/genetics/120.3.831. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johanson U., West J., Lister C., Michaels S., Amasino R., Dean C. Molecular analysis of FRIGIDA, a major determinant of natural variation in Arabidopsis flowering time. Science. 2000 Oct 13;290(5490):344–347. doi: 10.1126/science.290.5490.344. [DOI] [PubMed] [Google Scholar]
- Kaplan N. L., Darden T., Hudson R. R. The coalescent process in models with selection. Genetics. 1988 Nov;120(3):819–829. doi: 10.1093/genetics/120.3.819. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Kaplan N., Hudson R. R., Iizuka M. The coalescent process in models with selection, recombination and geographic subdivision. Genet Res. 1991 Feb;57(1):83–91. doi: 10.1017/s0016672300029074. [DOI] [PubMed] [Google Scholar]
- Kelly J. K., Wade M. J. Molecular evolution near a two-locus balanced polymorphism. J Theor Biol. 2000 May 7;204(1):83–101. doi: 10.1006/jtbi.2000.2003. [DOI] [PubMed] [Google Scholar]
- 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]
- Krone SM, Neuhauser C. Ancestral Processes with Selection. Theor Popul Biol. 1997 Jun;51(3):210–237. doi: 10.1006/tpbi.1997.1299. [DOI] [PubMed] [Google Scholar]
- Navarro Arcadio, Barton Nick H. The effects of multilocus balancing selection on neutral variability. Genetics. 2002 Jun;161(2):849–863. doi: 10.1093/genetics/161.2.849. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neuhauser C. The ancestral graph and gene genealogy under frequency-dependent selection. Theor Popul Biol. 1999 Oct;56(2):203–214. doi: 10.1006/tpbi.1999.1412. [DOI] [PubMed] [Google Scholar]
- Nordborg M. Structured coalescent processes on different time scales. Genetics. 1997 Aug;146(4):1501–1514. doi: 10.1093/genetics/146.4.1501. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Przeworski M., Wall J. D., Andolfatto P. Recombination and the frequency spectrum in Drosophila melanogaster and Drosophila simulans. Mol Biol Evol. 2001 Mar;18(3):291–298. doi: 10.1093/oxfordjournals.molbev.a003805. [DOI] [PubMed] [Google Scholar]
- Schierup M. H., Charlesworth D., Vekemans X. The effect of hitch-hiking on genes linked to a balanced polymorphism in a subdivided population. Genet Res. 2000 Aug;76(1):63–73. doi: 10.1017/s0016672300004547. [DOI] [PubMed] [Google Scholar]
- Schierup M. H., Mikkelsen A. M., Hein J. Recombination, balancing selection and phylogenies in MHC and self-incompatibility genes. Genetics. 2001 Dec;159(4):1833–1844. doi: 10.1093/genetics/159.4.1833. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Simonsen K. L., Churchill G. A., Aquadro C. F. Properties of statistical tests of neutrality for DNA polymorphism data. Genetics. 1995 Sep;141(1):413–429. doi: 10.1093/genetics/141.1.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Slade P. F. Most recent common ancestor probability distributions in gene genealogies under selection. Theor Popul Biol. 2000 Dec;58(4):291–305. doi: 10.1006/tpbi.2000.1488. [DOI] [PubMed] [Google Scholar]
- Slade P. F. Simulation of 'hitch-hiking' genealogies. J Math Biol. 2001 Jan;42(1):41–70. doi: 10.1007/pl00000072. [DOI] [PubMed] [Google Scholar]
- Slade P. F. Simulation of selected genealogies. Theor Popul Biol. 2000 Feb;57(1):35–49. doi: 10.1006/tpbi.1999.1438. [DOI] [PubMed] [Google Scholar]
- Stahl E. A., Dwyer G., Mauricio R., Kreitman M., Bergelson J. Dynamics of disease resistance polymorphism at the Rpm1 locus of Arabidopsis. Nature. 1999 Aug 12;400(6745):667–671. doi: 10.1038/23260. [DOI] [PubMed] [Google Scholar]
- 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]
- Takahata N. A simple genealogical structure of strongly balanced allelic lines and trans-species evolution of polymorphism. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2419–2423. doi: 10.1073/pnas.87.7.2419. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takahata N., Satta Y. Footprints of intragenic recombination at HLA loci. Immunogenetics. 1998 May;47(6):430–441. doi: 10.1007/s002510050380. [DOI] [PubMed] [Google Scholar]
- Tian Dacheng, Araki Hitoshi, Stahl Eli, Bergelson Joy, Kreitman Martin. Signature of balancing selection in Arabidopsis. Proc Natl Acad Sci U S A. 2002 Aug 9;99(17):11525–11530. doi: 10.1073/pnas.172203599. [DOI] [PMC free article] [PubMed] [Google Scholar]