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Genetics. Nov 1987; 117(3): 543–557.
PMCID: PMC1203229

Sequence-Dependent Gene Conversion: Can Duplicated Genes Diverge Fast Enough to Escape Conversion?

Abstract

Conversion between duplicated genes limits their independent evolution. Models in which conversion frequencies decrease as genes diverge are examined to determine conditions underwhich genes can "escape" further conversion and hence escape from a gene family. A review of results from various recombination systems suggests two classes of sequence-dependence models: (1) the "k-hit" model in which conversion is completely inactivated by a few (k) mutational events, such as the insertion of a mobile element, and (2) more general models where conversion frequency gradually declines as genes diverge through the accumulation of point mutants. Exact analysis of the k-hit model is given and an approximate analysis of a more general sequence-dependent model is developed and verified by computer simulation. If µ is the per nucleotide mutation rate, then neutral duplicated genes diverging through point mutants are likely to escape conversion provided 2µ/λ >> 0.1, where λ is the conversion rate between identical genes. If 2µ/λ << 0.1, the expected number of conversions before escape increases exponentially so that, for biological purposes, the genes never escape conversion. For single mutational events sufficient to block further conversions, occurring at rate ν per copy per generation, many conversions are expected if 2ν/λ << 1, while the genes essentially evolve independently if 2ν/λ >> 1. Implications of these results for both models of concerted evolution and the evolution of new gene functions via gene duplication are discussed.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Avery PJ, Hill WG. Variance in quantitative traits due to linked dominant genes and variance in heterozygosity in small populations. Genetics. 1979 Apr;91(4):817–844. [PMC free article] [PubMed]
  • Bulmer MG. The effect of selection on genetic variability: a simulation study. Genet Res. 1976 Oct;28(2):101–117. [PubMed]
  • Felsenstein J. The evolutionary advantage of recombination. Genetics. 1974 Oct;78(2):737–756. [PMC free article] [PubMed]
  • Kacser H, Burns JA. The control of flux. Symp Soc Exp Biol. 1973;27:65–104. [PubMed]
  • Kacser H, Burns JA. The molecular basis of dominance. Genetics. 1981 Mar-Apr;97(3-4):639–666. [PMC free article] [PubMed]
  • Keightley PD, Hill WG. Effects of linkage on response to directional selection from new mutations. Genet Res. 1983 Oct;42(2):193–206. [PubMed]
  • Mukai T, Chigusa SI, Mettler LE, Crow JF. Mutation rate and dominance of genes affecting viability in Drosophila melanogaster. Genetics. 1972 Oct;72(2):335–355. [PMC free article] [PubMed]
  • Balkau BJ, Feldman MW. Selection for migration modification. Genetics. 1973 May;74(1):171–174. [PMC free article] [PubMed]
  • Charlesworth B. Recombination modification in a flucturating environment. Genetics. 1976 May;83(1):181–195. [PMC free article] [PubMed]
  • Charlesworth D, Charlesworth B. Selection on recombination in a multi-locus system. Genetics. 1979 Mar;91(3):575–580. [PMC free article] [PubMed]
  • Charlesworth D, Charlesworth B. Selection on recombination in clines. Genetics. 1979 Mar;91(3):581–589. [PMC free article] [PubMed]
  • Charlesworth D, Charlesworth B, Strobeck C. Selection for recombination in partially self-fertilizing populations. Genetics. 1979 Sep;93(1):237–244. [PMC free article] [PubMed]
  • Christiansen FB, Feldman MW. Subdivided populations: a review of the one- and two-locus deterministic theory. Theor Popul Biol. 1975 Feb;7(1):13–38. [PubMed]
  • Feldman MW. Selection for linkage modification. I. Random mating populations. Theor Popul Biol. 1972 Sep;3(3):324–346. [PubMed]
  • Feldman MW, Balkau B. Selection for Linkage Modification II. a Recombination Balance for Neutral Modifiers. Genetics. 1973 Aug;74(4):713–726. [PMC free article] [PubMed]
  • Feldman MW, Christiansen FB, Brooks LD. Evolution of recombination in a constant environment. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4838–4841. [PMC free article] [PubMed]
  • Gillespie JH. Evolution of the mutation rate at a heterotic locus. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2452–2454. [PMC free article] [PubMed]
  • Holsinger KE, Feldman MW. Modifiers of mutation rate: Evolutionary optimum with complete selfing. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6732–6734. [PMC free article] [PubMed]
  • Holsinger KE, Feldman MW, Altenberg L. Selection for increased mutation rates with fertility differences between matings. Genetics. 1986 Apr;112(4):909–922. [PMC free article] [PubMed]
  • Karlin S, Carmelli D. Numerical studies on two-loci selection models with general viabilities. Theor Popul Biol. 1975 Jun;7(3):399–421. [PubMed]
  • Karlin S, McGregor J. Polymorphisms for genetic and ecological systems with weak coupling. Theor Popul Biol. 1972 Jun;3(2):210–238. [PubMed]
  • Strobeck C, Smith JM, Charlesworth B. The effects of hitchhiking on a gene for recombination. Genetics. 1976 Mar 25;82(3):547–558. [PMC free article] [PubMed]
  • Teague R. A result on the selection of recombination altering mechanisms. J Theor Biol. 1976 Jun;59(1):25–32. [PubMed]
  • Teague R. A model of migration modification. Theor Popul Biol. 1977 Aug;12(1):86–94. [PubMed]
  • Thomson GJ, Feldman MW. Population genetics of modifiers of meiotic drive. II. Linkage modification in the segregation distortion system. Theor Popul Biol. 1974 Apr;5(2):155–162. [PubMed]
  • von Wettstein D, Rasmussen SW, Holm PB. The synaptonemal complex in genetic segregation. Annu Rev Genet. 1984;18:331–413. [PubMed]
  • Prout T, Bundgaard J, Bryant S. Population genetics of modifiers of meiotic drive. I. The solution of a special case and some general implications. Theor Popul Biol. 1973 Dec;4(4):446–465. [PubMed]
  • Baba ML, Goodman M, Berger-Cohn J, Demaille JG, Matsuda G. The early adaptive evolution of calmodulin. Mol Biol Evol. 1984 Nov;1(6):442–455. [PubMed]
  • Blackwell TK, Moore MW, Yancopoulos GD, Suh H, Lutzker S, Selsing E, Alt FW. Recombination between immunoglobulin variable region gene segments is enhanced by transcription. Nature. 1986 Dec 11;324(6097):585–589. [PubMed]
  • Erhart MA, Simons KS, Weaver S. Evolution of the mouse beta-globin genes: a recent gene conversion in the Hbbs haplotype. Mol Biol Evol. 1985 Jul;2(4):304–320. [PubMed]
  • Fink GR, Petes TD. Gene conversion in the absence of reciprocal recombination. Nature. 310(5980):728–729. [PubMed]
  • Fischer JA, Maniatis T. Regulatory elements involved in Drosophila Adh gene expression are conserved in divergent species and separate elements mediate expression in different tissues. EMBO J. 1986 Jun;5(6):1275–1289. [PMC free article] [PubMed]
  • Flavell RA, Allen H, Burkly LC, Sherman DH, Waneck GL, Widera G. Molecular biology of the H-2 histocompatibility complex. Science. 1986 Jul 25;233(4762):437–443. [PubMed]
  • Baltimore D. Retroviruses and retrotransposons: the role of reverse transcription in shaping the eukaryotic genome. Cell. 1985 Mar;40(3):481–482. [PubMed]
  • Ferris SD, Whitt GS. Evolution of the differential regulation of duplicate genes after polyploidization. J Mol Evol. 1979 Apr 12;12(4):267–317. [PubMed]
  • Hess JF, Fox M, Schmid C, Shen CK. Molecular evolution of the human adult alpha-globin-like gene region: insertion and deletion of Alu family repeats and non-Alu DNA sequences. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5970–5974. [PMC free article] [PubMed]
  • Hill AV, Nicholls RD, Thein SL, Higgs DR. Recombination within the human embryonic xi-globin locus: a common xi-xi chromosome produced by gene conversion of the psi xi gene. Cell. 1985 Oct;42(3):809–819. [PubMed]
  • Hill RE, Shaw PH, Boyd PA, Baumann H, Hastie ND. Plasma protease inhibitors in mouse and man: divergence within the reactive centre regions. Nature. 1984 Sep 13;311(5982):175–177. [PubMed]
  • Hsieh P, Meyn MS, Camerini-Otero RD. Partial purification and characterization of a recombinase from human cells. Cell. 1986 Mar 28;44(6):885–894. [PubMed]
  • Ivell R, Richter D. Structure and comparison of the oxytocin and vasopressin genes from rat. Proc Natl Acad Sci U S A. 1984 Apr;81(7):2006–2010. [PMC free article] [PubMed]
  • Jasin M, de Villiers J, Weber F, Schaffner W. High frequency of homologous recombination in mammalian cells between endogenous and introduced SV40 genomes. Cell. 1985 Dec;43(3 Pt 2):695–703. [PubMed]
  • Keil RL, Roeder GS. Cis-acting, recombination-stimulating activity in a fragment of the ribosomal DNA of S. cerevisiae. Cell. 1984 Dec;39(2 Pt 1):377–386. [PubMed]
  • Klein HL. Lack of association between intrachromosomal gene conversion and reciprocal exchange. Nature. 310(5980):748–753. [PubMed]
  • Jinks-Robertson S, Petes TD. High-frequency meiotic gene conversion between repeated genes on nonhomologous chromosomes in yeast. Proc Natl Acad Sci U S A. 1985 May;82(10):3350–3354. [PMC free article] [PubMed]
  • Kmiec EB, Angelides KJ, Holloman WK. Left-handed DNA and the synaptic pairing reaction promoted by Ustilago rec1 protein. Cell. 1985 Jan;40(1):139–145. [PubMed]
  • Koch AL. Enzyme evolution. I. The importance of untranslatable intermediates. Genetics. 1972 Oct;72(2):297–316. [PMC free article] [PubMed]
  • Kostriken R, Strathern JN, Klar AJ, Hicks JB, Heffron F. A site-specific endonuclease essential for mating-type switching in Saccharomyces cerevisiae. Cell. 1983 Nov;35(1):167–174. [PubMed]
  • Krawinkel U, Zoebelein G, Bothwell AL. Palindromic sequences are associated with sites of DNA breakage during gene conversion. Nucleic Acids Res. 1986 May 12;14(9):3871–3882. [PMC free article] [PubMed]
  • Lefèvre JC, Gasc AM, Burger AC, Mostachfi P, Sicard AM. Hyperrecombination at a specific DNA sequence in pneumococcal transformation. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5184–5188. [PMC free article] [PubMed]
  • Lewis SA, Cowan NJ. Anomalous placement of introns in a member of the intermediate filament multigene family: an evolutionary conundrum. Mol Cell Biol. 1986 May;6(5):1529–1534. [PMC free article] [PubMed]
  • Lichten M, Borts RH, Haber JE. Meiotic gene conversion and crossing over between dispersed homologous sequences occurs frequently in Saccharomyces cerevisiae. Genetics. 1987 Feb;115(2):233–246. [PMC free article] [PubMed]
  • Liskay RM, Stachelek JL, Letsou A. Homologous recombination between repeated chromosomal sequences in mouse cells. Cold Spring Harb Symp Quant Biol. 1984;49:183–189. [PubMed]
  • McCarrey JR, Thomas K. Human testis-specific PGK gene lacks introns and possesses characteristics of a processed gene. Nature. 1987 Apr 2;326(6112):501–505. [PubMed]
  • McIntyre KR, Seidman JG. Nucleotide sequence of mutant I-A beta bm12 gene is evidence for genetic exchange between mouse immune response genes. Nature. 1984 Apr 5;308(5959):551–553. [PubMed]
  • Markham P, Whitehouse HL. A hypothesis for the initiation of genetic recombination in eukaryotes. Nature. 1982 Feb 4;295(5848):421–423. [PubMed]
  • Meselson MS, Radding CM. A general model for genetic recombination. Proc Natl Acad Sci U S A. 1975 Jan;72(1):358–361. [PMC free article] [PubMed]
  • Mills LE, Batterham P, Alegre J, Starmer WT, Sullivan DT. Molecular genetic characterization of a locus that contains duplicate Adh genes in Drosophila mojavensis and related species. Genetics. 1986 Feb;112(2):295–310. [PMC free article] [PubMed]
  • Ohta T. On the evolution of multigene families. Theor Popul Biol. 1983 Apr;23(2):216–240. [PubMed]
  • Ohta T. Simulating evolution by gene duplication. Genetics. 1987 Jan;115(1):207–213. [PMC free article] [PubMed]
  • Pays E, Houard S, Pays A, Van Assel S, Dupont F, Aerts D, Huet-Duvillier G, Gomés V, Richet C, Degand P, et al. Trypanosoma brucei: the extent of conversion in antigen genes may be related to the DNA coding specificity. Cell. 1985 Oct;42(3):821–829. [PubMed]
  • Powers PA, Smithies O. Short gene conversions in the human fetal globin gene region: a by-product of chromosome pairing during meiosis? Genetics. 1986 Feb;112(2):343–358. [PMC free article] [PubMed]
  • Reynaud CA, Anquez V, Grimal H, Weill JC. A hyperconversion mechanism generates the chicken light chain preimmune repertoire. Cell. 1987 Feb 13;48(3):379–388. [PubMed]
  • Rigby PW, Burleigh BD, Jr, Hartley BS. Gene duplication in experimental enzyme evolution. Nature. 1974 Sep 20;251(5472):200–204. [PubMed]
  • Rubnitz J, Subramani S. Extrachromosomal and chromosomal gene conversion in mammalian cells. Mol Cell Biol. 1986 May;6(5):1608–1614. [PMC free article] [PubMed]
  • Ruppert S, Scherer G, Schütz G. Recent gene conversion involving bovine vasopressin and oxytocin precursor genes suggested by nucleotide sequence. Nature. 1984 Apr 5;308(5959):554–557. [PubMed]
  • Shen P, Huang HV. Homologous recombination in Escherichia coli: dependence on substrate length and homology. Genetics. 1986 Mar;112(3):441–457. [PMC free article] [PubMed]
  • Singer BS, Gold L, Gauss P, Doherty DH. Determination of the amount of homology required for recombination in bacteriophage T4. Cell. 1982 Nov;31(1):25–33. [PubMed]
  • Slightom JL, Blechl AE, Smithies O. Human fetal G gamma- and A gamma-globin genes: complete nucleotide sequences suggest that DNA can be exchanged between these duplicated genes. Cell. 1980 Oct;21(3):627–638. [PubMed]
  • Slightom JL, Chang LY, Koop BF, Goodman M. Chimpanzee fetal G gamma and A gamma globin gene nucleotide sequences provide further evidence of gene conversions in hominine evolution. Mol Biol Evol. 1985 Sep;2(5):370–389. [PubMed]
  • Soares MB, Schon E, Henderson A, Karathanasis SK, Cate R, Zeitlin S, Chirgwin J, Efstratiadis A. RNA-mediated gene duplication: the rat preproinsulin I gene is a functional retroposon. Mol Cell Biol. 1985 Aug;5(8):2090–2103. [PMC free article] [PubMed]
  • Stein JP, Munjaal RP, Lagace L, Lai EC, O'Malley BW, Means AR. Tissue-specific expression of a chicken calmodulin pseudogene lacking intervening sequences. Proc Natl Acad Sci U S A. 1983 Nov;80(21):6485–6489. [PMC free article] [PubMed]
  • Steinmetz M, Stephan D, Fischer Lindahl K. Gene organization and recombinational hotspots in the murine major histocompatibility complex. Cell. 1986 Mar 28;44(6):895–904. [PubMed]
  • Szostak JW, Orr-Weaver TL, Rothstein RJ, Stahl FW. The double-strand-break repair model for recombination. Cell. 1983 May;33(1):25–35. [PubMed]
  • Vanin EF. Processed pseudogenes: characteristics and evolution. Annu Rev Genet. 1985;19:253–272. [PubMed]
  • Voelkel-Meiman K, Keil RL, Roeder GS. Recombination-stimulating sequences in yeast ribosomal DNA correspond to sequences regulating transcription by RNA polymerase I. Cell. 1987 Mar 27;48(6):1071–1079. [PubMed]
  • Walsh JB. How many processed pseudogenes are accumulated in a gene family? Genetics. 1985 Jun;110(2):345–364. [PMC free article] [PubMed]
  • Watt VM, Ingles CJ, Urdea MS, Rutter WJ. Homology requirements for recombination in Escherichia coli. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4768–4772. [PMC free article] [PubMed]
  • Wilson AC, Carlson SS, White TJ. Biochemical evolution. Annu Rev Biochem. 1977;46:573–639. [PubMed]
  • Wistow GJ, Mulders JW, de Jong WW. The enzyme lactate dehydrogenase as a structural protein in avian and crocodilian lenses. Nature. 1987 Apr 9;326(6113):622–624. [PubMed]

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