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. 2000 Jun;155(2):685–698. doi: 10.1093/genetics/155.2.685

Effect of inversion polymorphism on the neutral nucleotide variability of linked chromosomal regions in Drosophila.

A Navarro 1, A Barbadilla 1, A Ruiz 1
PMCID: PMC1461098  PMID: 10835391

Abstract

Recombination is a main factor determining nucleotide variability in different regions of the genome. Chromosomal inversions, which are ubiquitous in the genus Drosophila, are known to reduce and redistribute recombination, and thus their specific effect on nucleotide variation may be of major importance as an explanatory factor for levels of DNA variation. Here, we use the coalescent approach to study this effect. First, we develop analytical expressions to predict nucleotide variability in old inversion polymorphisms that have reached mutation-drift-flux equilibrium. The effects on nucleotide variability of a new arrangement appearing in the population and reaching a stable polymorphism are then studied by computer simulation. We show that inversions modulate nucleotide variability in a complex way. The establishment of an inversion polymorphism involves a partial selective sweep that eliminates part of the variability in the population. This is followed by a slow convergence to the equilibrium values. During this convergence, regions close to the breakpoints exhibit much lower variability than central regions. However, at equilibrium, regions close to the breakpoints have higher levels of variability and differentiation between arrangements than regions in the middle of the inverted segment. The implications of these findings for overall variability levels during the evolution of Drosophila species are discussed.

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Selected References

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  1. Aguade M. Restriction map variation at the adh locus of Drosophila melanogaster in inverted and noninverted chromosomes. Genetics. 1988 May;119(1):135–140. doi: 10.1093/genetics/119.1.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Akashi H. Molecular evolution between Drosophila melanogaster and D. simulans: reduced codon bias, faster rates of amino acid substitution, and larger proteins in D. melanogaster. Genetics. 1996 Nov;144(3):1297–1307. doi: 10.1093/genetics/144.3.1297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Aquadro C. F., Desse S. F., Bland M. M., Langley C. H., Laurie-Ahlberg C. C. Molecular population genetics of the alcohol dehydrogenase gene region of Drosophila melanogaster. Genetics. 1986 Dec;114(4):1165–1190. doi: 10.1093/genetics/114.4.1165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Bénassi V., Aulard S., Mazeau S., Veuille M. Molecular variation of Adh and P6 genes in an African population of Drosophila melanogaster and its relation to chromosomal inversions. Genetics. 1993 Jul;134(3):789–799. doi: 10.1093/genetics/134.3.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Charlesworth B. Inversion polymorphism in a two-locus genetic system. Genet Res. 1974 Jun;23(3):259–280. doi: 10.1017/s0016672300014919. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Charlesworth B. The effect of background selection against deleterious mutations on weakly selected, linked variants. Genet Res. 1994 Jun;63(3):213–227. doi: 10.1017/s0016672300032365. [DOI] [PubMed] [Google Scholar]
  11. Chovnick A. Gene conversion and transfer of genetic information within the inverted region of inversion heterozygotes. Genetics. 1973 Sep;75(1):123–131. doi: 10.1093/genetics/75.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cáceres M., Ranz J. M., Barbadilla A., Long M., Ruiz A. Generation of a widespread Drosophila inversion by a transposable element. Science. 1999 Jul 16;285(5426):415–418. doi: 10.1126/science.285.5426.415. [DOI] [PubMed] [Google Scholar]
  13. Depaulis F., Brazier L., Veuille M. Selective sweep at the Drosophila melanogaster Suppressor of Hairless locus and its association with the In(2L)t inversion polymorphism. Genetics. 1999 Jul;152(3):1017–1024. doi: 10.1093/genetics/152.3.1017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dobbs DA, Vanhessche KP, Brazi E, Rautenstrauch V, V, Lenoir JY, Genêt JP, Wiles J, Bergens SH. Industrial Synthesis of (+)-cis-Methyl Dihydrojasmonate by Enantioselective Catalytic Hydrogenation; Identification of the Precatalyst. Angew Chem Int Ed Engl. 2000 Jun 2;39(11):1992–1995. doi: 10.1002/1521-3773(20000602)39:11<1992::aid-anie1992>3.0.co;2-w. [DOI] [PubMed] [Google Scholar]
  15. Hasson E., Eanes W. F. Contrasting histories of three gene regions associated with In(3L)Payne of Drosophila melanogaster. Genetics. 1996 Dec;144(4):1565–1575. doi: 10.1093/genetics/144.4.1565. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. Hudson R. R. Properties of a neutral allele model with intragenic recombination. Theor Popul Biol. 1983 Apr;23(2):183–201. doi: 10.1016/0040-5809(83)90013-8. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Kimura M. The rate of molecular evolution considered from the standpoint of population genetics. Proc Natl Acad Sci U S A. 1969 Aug;63(4):1181–1188. doi: 10.1073/pnas.63.4.1181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kreitman M., Wayne M. L. Organization of genetic variation at the molecular level: lessons from Drosophila. EXS. 1994;69:157–183. doi: 10.1007/978-3-0348-7527-1_9. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Moriyama E. N., Powell J. R. Intraspecific nuclear DNA variation in Drosophila. Mol Biol Evol. 1996 Jan;13(1):261–277. doi: 10.1093/oxfordjournals.molbev.a025563. [DOI] [PubMed] [Google Scholar]
  24. Nachman M. W., Bauer V. L., Crowell S. L., Aquadro C. F. DNA variability and recombination rates at X-linked loci in humans. Genetics. 1998 Nov;150(3):1133–1141. doi: 10.1093/genetics/150.3.1133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Nachman M. W. Patterns of DNA variability at X-linked loci in Mus domesticus. Genetics. 1997 Nov;147(3):1303–1316. doi: 10.1093/genetics/147.3.1303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Nagylaki T. Geographical invariance in population genetics. J Theor Biol. 1982 Nov 7;99(1):159–172. doi: 10.1016/0022-5193(82)90396-4. [DOI] [PubMed] [Google Scholar]
  27. Navarro A., Betrán E., Barbadilla A., Ruiz A. Recombination and gene flux caused by gene conversion and crossing over in inversion heterokaryotypes. Genetics. 1997 Jun;146(2):695–709. doi: 10.1093/genetics/146.2.695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Navarro A., Betrán E., Zapata C., Ruiz A. Dynamics of gametic disequilibria between loci linked to chromosome inversions: the recombination-redistributing effect of inversions. Genet Res. 1996 Feb;67(1):67–76. doi: 10.1017/s0016672300033486. [DOI] [PubMed] [Google Scholar]
  29. Navarro A., Ruiz A. On the fertility effects of pericentric inversions. Genetics. 1997 Oct;147(2):931–933. doi: 10.1093/genetics/147.2.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Nei M., Kojima K. I., Schaffer H. E. Frequency changes of new inversions in populations under mutation-selection equilibria. Genetics. 1967 Dec;57(4):741–750. doi: 10.1093/genetics/57.4.741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. Notohara M. The coalescent and the genealogical process in geographically structured population. J Math Biol. 1990;29(1):59–75. doi: 10.1007/BF00173909. [DOI] [PubMed] [Google Scholar]
  33. Ohta T., Kojima K. I. Survival probabilities f new inversions in large populations. Biometrics. 1968 Sep;24(3):501–516. [PubMed] [Google Scholar]
  34. Payne F. Crossover Modifiers in the Third Chromosome of DROSOPHILA MELANOGASTER. Genetics. 1924 Jul;9(4):327–342. doi: 10.1093/genetics/9.4.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Popadić A., Anderson W. W. Evidence for gene conversion in the amylase multigene family of Drosophila pseudoobscura. Mol Biol Evol. 1995 Jul;12(4):564–572. doi: 10.1093/oxfordjournals.molbev.a040236. [DOI] [PubMed] [Google Scholar]
  36. Popadić A., Popadić D., Anderson W. W. Interchromosomal exchange of genetic information between gene arrangements on the third chromosome of Drosophila pseudoobscura. Mol Biol Evol. 1995 Sep;12(5):938–943. doi: 10.1093/oxfordjournals.molbev.a040271. [DOI] [PubMed] [Google Scholar]
  37. Prakash S., Lewontin R. C. A molecular approach to the study of genic heterozygosity in natural populations. 3. Direct evidence of coadaptation in gene arrangements of Drosophila. Proc Natl Acad Sci U S A. 1968 Feb;59(2):398–405. doi: 10.1073/pnas.59.2.398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Ranz J. M., Cáceres M., Ruiz A. Comparative mapping of cosmids and gene clones from a 1.6 Mb chromosomal region of Drosophila melanogaster in three species of the distantly related subgenus Drosophila. Chromosoma. 1999 Apr;108(1):32–43. doi: 10.1007/s004120050349. [DOI] [PubMed] [Google Scholar]
  39. Ranz J. M., Segarra C., Ruiz A. Chromosomal homology and molecular organization of Muller's elements D and E in the Drosophila repleta species group. Genetics. 1997 Feb;145(2):281–295. doi: 10.1093/genetics/145.2.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Rozas J., Aguadé M. Gene conversion is involved in the transfer of genetic information between naturally occurring inversions of Drosophila. Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11517–11521. doi: 10.1073/pnas.91.24.11517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rozas J., Aguadé M. Transfer of genetic information in the rp49 region of Drosophila subobscura between different chromosomal gene arrangements. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8083–8087. doi: 10.1073/pnas.90.17.8083. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Rozas J., Segarra C., Ribó G., Aguadé M. Molecular population genetics of the rp49 gene region in different chromosomal inversions of Drosophila subobscura. Genetics. 1999 Jan;151(1):189–202. doi: 10.1093/genetics/151.1.189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Slatkin M. The average number of sites separating DNA sequences drawn from a subdivided population. Theor Popul Biol. 1987 Aug;32(1):42–49. doi: 10.1016/0040-5809(87)90038-4. [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. 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]
  46. Sturtevant A H, Beadle G W. The Relations of Inversions in the X Chromosome of Drosophila Melanogaster to Crossing over and Disjunction. Genetics. 1936 Sep;21(5):554–604. doi: 10.1093/genetics/21.5.554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Tajima F. DNA polymorphism in a subdivided population: the expected number of segregating sites in the two-subpopulation model. Genetics. 1989 Sep;123(1):229–240. doi: 10.1093/genetics/123.1.229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Tajima F. Evolutionary relationship of DNA sequences in finite populations. Genetics. 1983 Oct;105(2):437–460. doi: 10.1093/genetics/105.2.437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. 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]
  50. True J. R., Mercer J. M., Laurie C. C. Differences in crossover frequency and distribution among three sibling species of Drosophila. Genetics. 1996 Feb;142(2):507–523. doi: 10.1093/genetics/142.2.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Wakeley J. The variance of pairwise nucleotide differences in two populations with migration. Theor Popul Biol. 1996 Feb;49(1):39–57. doi: 10.1006/tpbi.1996.0002. [DOI] [PubMed] [Google Scholar]
  52. 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]
  53. Wesley C. S., Eanes W. F. Isolation and analysis of the breakpoint sequences of chromosome inversion In(3L)Payne in Drosophila melanogaster. Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3132–3136. doi: 10.1073/pnas.91.8.3132. [DOI] [PMC free article] [PubMed] [Google Scholar]

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