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. 2003 Nov;165(3):1195–1208. doi: 10.1093/genetics/165.3.1195

Recombination, dominance and selection on amino acid polymorphism in the Drosophila genome: contrasting patterns on the X and fourth chromosomes.

Lea A Sheldahl 1, Daniel M Weinreich 1, David M Rand 1
PMCID: PMC1462837  PMID: 14668375

Abstract

Surveys of nucleotide polymorphism and divergence indicate that the average selection coefficient on Drosophila proteins is weakly positive. Similar surveys in mitochondrial genomes and in the selfing plant Arabidopsis show that weak negative selection has operated. These differences have been attributed to the low recombination environment of mtDNA and Arabidopsis that has hindered adaptive evolution through the interference effects of linkage. We test this hypothesis with new sequence surveys of proteins lying in low recombination regions of the Drosophila genome. We surveyed >3800 bp across four proteins at the tip of the X chromosome and >3600 bp across four proteins on the fourth chromosome in 24 strains of D. melanogaster and 5 strains of D. simulans. This design seeks to study the interaction of selection and linkage by comparing silent and replacement variation in semihaploid (X chromosome) and diploid (fourth chromosome) environments lying in regions of low recombination. While the data do indicate very low rates of exchange, all four gametic phases were observed both at the tip of the X and across the fourth chromosome. Silent variation is very low at the tip of the X (thetaS = 0.0015) and on the fourth chromosome (thetaS = 0.0002), but the tip of the X shows a greater proportional loss of variation than the fourth shows relative to normal-recombination regions. In contrast, replacement polymorphism at the tip of the X is not reduced (thetaR = 0.00065, very close to the X chromosome average). MK and HKA tests both indicate a significant excess of amino acid polymorphism at the tip of the X relative to the fourth. Selection is significantly negative at the tip of the X (Nes = -1.53) and nonsignificantly positive on the fourth (Nes approximately 2.9), analogous to the difference between mtDNA (or Arabidopsis) and the Drosophila genome average. Our distal X data are distinct from regions of normal recombination where the X shows a deficiency of amino acid polymorphism relative to the autosomes, suggesting more efficient selection against recessive deleterious replacement mutations. We suggest that the excess amino acid polymorphism on the distal X relative to the fourth chromosome is due to (1) differences in the mutation rate for selected mutations on the distal X or (2) a greater relaxation of selection from stronger linkage-related interference effects on the distal X. This relaxation of selection is presumed to be greater in magnitude than the difference in efficiency of selection between X-linked vs. autosomal selection.

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Selected References

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  1. Adams M. D., Celniker S. E., Holt R. A., Evans C. A., Gocayne J. D., Amanatides P. G., Scherer S. E., Li P. W., Hoskins R. A., Galle R. F. The genome sequence of Drosophila melanogaster. Science. 2000 Mar 24;287(5461):2185–2195. doi: 10.1126/science.287.5461.2185. [DOI] [PubMed] [Google Scholar]
  2. Aguade M., Miyashita N., Langley C. H. Reduced variation in the yellow-achaete-scute region in natural populations of Drosophila melanogaster. Genetics. 1989 Jul;122(3):607–615. doi: 10.1093/genetics/122.3.607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Akashi H. Inferring weak selection from patterns of polymorphism and divergence at "silent" sites in Drosophila DNA. Genetics. 1995 Feb;139(2):1067–1076. doi: 10.1093/genetics/139.2.1067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Ballard J. W. Comparative genomics of mitochondrial DNA in members of the Drosophila melanogaster subgroup. J Mol Evol. 2000 Jul;51(1):48–63. doi: 10.1007/s002390010066. [DOI] [PubMed] [Google Scholar]
  6. Begun D. J., Aquadro C. F. Evolutionary inferences from DNA variation at the 6-phosphogluconate dehydrogenase locus in natural populations of drosophila: selection and geographic differentiation. Genetics. 1994 Jan;136(1):155–171. doi: 10.1093/genetics/136.1.155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Begun D. J., Aquadro C. F. Molecular population genetics of the distal portion of the X chromosome in Drosophila: evidence for genetic hitchhiking of the yellow-achaete region. Genetics. 1991 Dec;129(4):1147–1158. doi: 10.1093/genetics/129.4.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Begun D. J. Population genetics of silent and replacement variation in Drosophila simulans and D. melanogaster: X/autosome differences? Mol Biol Evol. 1996 Dec;13(10):1405–1407. doi: 10.1093/oxfordjournals.molbev.a025587. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Berry A. J., Ajioka J. W., Kreitman M. Lack of polymorphism on the Drosophila fourth chromosome resulting from selection. Genetics. 1991 Dec;129(4):1111–1117. doi: 10.1093/genetics/129.4.1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Bustamante Carlos D., Nielsen Rasmus, Sawyer Stanley A., Olsen Kenneth M., Purugganan Michael D., Hartl Daniel L. The cost of inbreeding in Arabidopsis. Nature. 2002 Apr 4;416(6880):531–534. doi: 10.1038/416531a. [DOI] [PubMed] [Google Scholar]
  14. Charlesworth B. Measures of divergence between populations and the effect of forces that reduce variability. Mol Biol Evol. 1998 May;15(5):538–543. doi: 10.1093/oxfordjournals.molbev.a025953. [DOI] [PubMed] [Google Scholar]
  15. Comeron J. M., Kreitman M., Aguadé M. Natural selection on synonymous sites is correlated with gene length and recombination in Drosophila. Genetics. 1999 Jan;151(1):239–249. doi: 10.1093/genetics/151.1.239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Fay Justin C., Wyckoff Gerald J., Wu Chung-I. Testing the neutral theory of molecular evolution with genomic data from Drosophila. Nature. 2002 Feb 28;415(6875):1024–1026. doi: 10.1038/4151024a. [DOI] [PubMed] [Google Scholar]
  18. Felsenstein J. The evolutionary advantage of recombination. Genetics. 1974 Oct;78(2):737–756. doi: 10.1093/genetics/78.2.737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Gillespie J. H. Genetic drift in an infinite population. The pseudohitchhiking model. Genetics. 2000 Jun;155(2):909–919. doi: 10.1093/genetics/155.2.909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gillespie J. H. Junk ain't what junk does: neutral alleles in a selected context. Gene. 1997 Dec 31;205(1-2):291–299. doi: 10.1016/s0378-1119(97)00470-8. [DOI] [PubMed] [Google Scholar]
  22. Hey Jody, Kliman Richard M. Interactions between natural selection, recombination and gene density in the genes of Drosophila. Genetics. 2002 Feb;160(2):595–608. doi: 10.1093/genetics/160.2.595. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hudson R. R., Boos D. D., Kaplan N. L. A statistical test for detecting geographic subdivision. Mol Biol Evol. 1992 Jan;9(1):138–151. doi: 10.1093/oxfordjournals.molbev.a040703. [DOI] [PubMed] [Google Scholar]
  24. Hudson R. R., Kaplan N. L. Statistical properties of the number of recombination events in the history of a sample of DNA sequences. Genetics. 1985 Sep;111(1):147–164. doi: 10.1093/genetics/111.1.147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. 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]
  28. 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]
  29. 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]
  30. 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]
  31. Malcom Christine M., Wyckoff Gerald J., Lahn Bruce T. Genic mutation rates in mammals: local similarity, chromosomal heterogeneity, and X-versus-autosome disparity. Mol Biol Evol. 2003 Jul 28;20(10):1633–1641. doi: 10.1093/molbev/msg178. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. McDonald J. H., Kreitman M. Adaptive protein evolution at the Adh locus in Drosophila. Nature. 1991 Jun 20;351(6328):652–654. doi: 10.1038/351652a0. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Nachman M. W. Deleterious mutations in animal mitochondrial DNA. Genetica. 1998;102-103(1-6):61–69. [PubMed] [Google Scholar]
  36. Payseur B. A., Nachman M. W. Microsatellite variation and recombination rate in the human genome. Genetics. 2000 Nov;156(3):1285–1298. doi: 10.1093/genetics/156.3.1285. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Rand D. M., Kann L. M. Excess amino acid polymorphism in mitochondrial DNA: contrasts among genes from Drosophila, mice, and humans. Mol Biol Evol. 1996 Jul;13(6):735–748. doi: 10.1093/oxfordjournals.molbev.a025634. [DOI] [PubMed] [Google Scholar]
  38. Rand D. M., Kann L. M. Mutation and selection at silent and replacement sites in the evolution of animal mitochondrial DNA. Genetica. 1998;102-103(1-6):393–407. [PubMed] [Google Scholar]
  39. Rand D. M., Weinreich D. M., Cezairliyan B. O. Neutrality tests of conservative-radical amino acid changes in nuclear- and mitochondrially-encoded proteins. Gene. 2000 Dec 30;261(1):115–125. doi: 10.1016/s0378-1119(00)00483-2. [DOI] [PubMed] [Google Scholar]
  40. Sawyer S. A., Hartl D. L. Population genetics of polymorphism and divergence. Genetics. 1992 Dec;132(4):1161–1176. doi: 10.1093/genetics/132.4.1161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. 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]
  42. Smith J. M., Haigh J. The hitch-hiking effect of a favourable gene. Genet Res. 1974 Feb;23(1):23–35. [PubMed] [Google Scholar]
  43. Solignac M., Monnerot M., Mounolou J. C. Mitochondrial DNA evolution in the melanogaster species subgroup of Drosophila. J Mol Evol. 1986;23(1):31–40. doi: 10.1007/BF02100996. [DOI] [PubMed] [Google Scholar]
  44. Stephan W., Langley C. H. DNA polymorphism in lycopersicon and crossing-over per physical length. Genetics. 1998 Dec;150(4):1585–1593. doi: 10.1093/genetics/150.4.1585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. 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]
  46. Wang Wen, Thornton Kevin, Berry Andrew, Long Manyuan. Nucleotide variation along the Drosophila melanogaster fourth chromosome. Science. 2002 Jan 4;295(5552):134–137. doi: 10.1126/science.1064521. [DOI] [PubMed] [Google Scholar]
  47. Wyckoff G. J., Wang W., Wu C. I. Rapid evolution of male reproductive genes in the descent of man. Nature. 2000 Jan 20;403(6767):304–309. doi: 10.1038/35002070. [DOI] [PubMed] [Google Scholar]

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