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. 1995 Dec;141(4):1619–1632. doi: 10.1093/genetics/141.4.1619

The Pattern of Neutral Molecular Variation under the Background Selection Model

D Charlesworth 1, B Charlesworth 1, M T Morgan 1
PMCID: PMC1206892  PMID: 8601499

Abstract

Stochastic simulations of the infinite sites model were used to study the behavior of genetic diversity at a neutral locus in a genomic region without recombination, but subject to selection against deleterious alleles maintained by recurrent mutation (background selection). In large populations, the effect of background selection on the number of segregating sites approaches the effct on nucleotide site diversity, i.e., the reduction in genetic variability caused by background selection resembles that caused by a simple reduction in effective population size. We examined, by coalescence-based methods, the power of several tests for the departure from neutral expectation of the frequency spectra of alleles in samples from randomly mating populations (TAJIMA's, FU and LI's, and WATTERSON's tests). All of the tests have low power unless the selection against mutant alleles is extremely weak. In Drosophila, significant TAJIMA's tests are usually not obtained with empirical data sets from loci in genomic regions with restricted recombination frequencies and that exhibit low genetic diversity. This is consistent with the operation of background selection as opposed to selective sweeps. It remains to be decided whether background selection is sufficient to explain the observed extent of reduction in diversity in regions of restricted recombination.

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Selected References

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  1. Aguadé M., Meyers W., Long A. D., Langley C. H. Single-strand conformation polymorphism analysis coupled with stratified DNA sequencing reveals reduced sequence variation in the su(s) and su(wa) regions of the Drosophila melanogaster X chromosome. Proc Natl Acad Sci U S A. 1994 May 24;91(11):4658–4662. doi: 10.1073/pnas.91.11.4658. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barton N. H. Linkage and the limits to natural selection. Genetics. 1995 Jun;140(2):821–841. doi: 10.1093/genetics/140.2.821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Charlesworth B., Lapid A., Canada D. The distribution of transposable elements within and between chromosomes in a population of Drosophila melanogaster. II. Inferences on the nature of selection against elements. Genet Res. 1992 Oct;60(2):115–130. doi: 10.1017/s0016672300030809. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Charlesworth B. Mutation-selection balance and the evolutionary advantage of sex and recombination. Genet Res. 1990 Jun;55(3):199–221. doi: 10.1017/s0016672300025532. [DOI] [PubMed] [Google Scholar]
  8. Ewens W. J. The sampling theory of selectively neutral alleles. Theor Popul Biol. 1972 Mar;3(1):87–112. doi: 10.1016/0040-5809(72)90035-4. [DOI] [PubMed] [Google Scholar]
  9. Fu Y. X., Li W. H. Statistical tests of neutrality of mutations. Genetics. 1993 Mar;133(3):693–709. doi: 10.1093/genetics/133.3.693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hanfstingl U., Berry A., Kellogg E. A., Costa J. T., 3rd, Rüdiger W., Ausubel F. M. Haplotypic divergence coupled with lack of diversity at the Arabidopsis thaliana alcohol dehydrogenase locus: roles for both balancing and directional selection? Genetics. 1994 Nov;138(3):811–828. doi: 10.1093/genetics/138.3.811. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Hudson R. R. How can the low levels of DNA sequence variation in regions of the drosophila genome with low recombination rates be explained? Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):6815–6818. doi: 10.1073/pnas.91.15.6815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kimura M., Maruyama T. The mutational load with epistatic gene interactions in fitness. Genetics. 1966 Dec;54(6):1337–1351. doi: 10.1093/genetics/54.6.1337. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kimura M., Takahata N. Selective constraint in protein polymorphism: study of the effectively neutral mutation model by using an improved pseudosampling method. Proc Natl Acad Sci U S A. 1983 Feb;80(4):1048–1052. doi: 10.1073/pnas.80.4.1048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Kondrashov A. S. Deleterious mutations and the evolution of sexual reproduction. Nature. 1988 Dec 1;336(6198):435–440. doi: 10.1038/336435a0. [DOI] [PubMed] [Google Scholar]
  17. Langley C. H., Montgomery E., Hudson R., Kaplan N., Charlesworth B. On the role of unequal exchange in the containment of transposable element copy number. Genet Res. 1988 Dec;52(3):223–235. doi: 10.1017/s0016672300027695. [DOI] [PubMed] [Google Scholar]
  18. Leicht B. G., Muse S. V., Hanczyc M., Clark A. G. Constraints on intron evolution in the gene encoding the myosin alkali light chain in Drosophila. Genetics. 1995 Jan;139(1):299–308. doi: 10.1093/genetics/139.1.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. MUKAI T. THE GENETIC STRUCTURE OF NATURAL POPULATIONS OF DROSOPHILA MELANOGASTER. I. SPONTANEOUS MUTATION RATE OF POLYGENES CONTROLLING VIABILITY. Genetics. 1964 Jul;50:1–19. doi: 10.1093/genetics/50.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Peck J. R. A ruby in the rubbish: beneficial mutations, deleterious mutations and the evolution of sex. Genetics. 1994 Jun;137(2):597–606. doi: 10.1093/genetics/137.2.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schoen D. J., Brown A. H. Intraspecific variation in population gene diversity and effective population size correlates with the mating system in plants. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4494–4497. doi: 10.1073/pnas.88.10.4494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Simmons G. M., Kwok W., Matulonis P., Venkatesh T. Polymorphism and divergence at the prune locus in Drosophila melanogaster and D. simulans. Mol Biol Evol. 1994 Jul;11(4):666–671. doi: 10.1093/oxfordjournals.molbev.a040145. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Slatkin M. An exact test for neutrality based on the Ewens sampling distribution. Genet Res. 1994 Aug;64(1):71–74. doi: 10.1017/s0016672300032560. [DOI] [PubMed] [Google Scholar]
  25. Strobeck C. Average number of nucleotide differences in a sample from a single subpopulation: a test for population subdivision. Genetics. 1987 Sep;117(1):149–153. doi: 10.1093/genetics/117.1.149. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Watterson G. A. Heterosis or neutrality? Genetics. 1977 Apr;85(4):789–814. doi: 10.1093/genetics/85.4.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Watterson G. A. The homozygosity test of neutrality. Genetics. 1978 Feb;88(2):405–417. doi: 10.1093/genetics/88.2.405. [DOI] [PMC free article] [PubMed] [Google Scholar]

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