Journal of Molecular Evolution

, Volume 68, Issue 4, pp 337–350 | Cite as

Duplicate Gene Evolution Toward Multiple Fates at the Drosophila melanogaster HIP/HIP-Replacement Locus



Hsc/Hsp70-interacting protein (HIP) is a rapidly evolving Hsp70 cofactor. Analyses of multiple Drosophila species indicate that the HIP gene is duplicated only in D. melanogaster. The HIP region, in fact, contains seven distinctly evolving duplicated genes. The regional duplication occurred in two steps, fixed rapidly, and illustrates multiple modes of duplicate gene evolution. HIP and its duplicate HIP-R are adaptively evolving in a manner unique to the region: they exhibit elevated divergence from other drosophilids and low polymorphism within D. melanogaster. HIP and HIP-R are virtually identical, share polymorphisms, and are subject to gene conversion. In contrast, two other duplicate genes in the region, CG33221 and GP-CG32779, are pseudogenes, and the chimeric gene Crg1 is subject to balancing selection. HIP and HIP-R are evolving rapidly and adaptively; however, positive selection is not sufficient to explain the molecular evolution of the region as a whole.


Hsc/Hsp70-interacting protein Gene duplication Concerted evolution Neofunctionalization 



We thank M. V. Graves and M. Nimali for their technical assistance. We are also grateful to D. L. Falcone, K. L. Montooth, and three anonymous reviewers for their helpful comments on an early version of the manuscript. This work was funded by the Commonwealth of Massachusetts and by Grant W911NF-06-1-0203 from the U.S. Army Research Office to B.R.B.

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  1. Bergthorsson U, Andersson DI, Roth JR (2007) Ohno’s dilemma: evolution of new genes under continuous selection. Proc Natl Acad Sci USA 104:17004–17009PubMedCrossRefGoogle Scholar
  2. Bethke LL, Zilversmit M, Neilsen K, Daily J, Volkman SK, Ndiaye D, Lozovsky ER, Hartl DL, Wirth DF (2006) Duplication, gene conversion, and genetic diversity in the species-specific acyl-CoA synthetase gene family of Plasmodium falciparum. Mol Biochem Parasitol 150:10–24PubMedCrossRefGoogle Scholar
  3. Bettencourt BR (2001) Molecular and phenotypic adaptation of Hsp70 and thermotolerance in Drosophila. Doctoral dissertation. University of ChicagoGoogle Scholar
  4. Bettencourt BR, Feder ME (2002) Rapid concerted evolution via gene conversion at the Drosophila hsp70 genes. J Mol Evol 54:569–586PubMedCrossRefGoogle Scholar
  5. Bettencourt BR, Hogan CC, Nimali M (2007) Polyglutamine expansion in Drosophila: thermal stress and Hsp70 as selective agents. J Biosci 32:537–547PubMedCrossRefGoogle Scholar
  6. Bettencourt BR, Hogan CC, Nimali M, Drohan BW (2008) Inducible and constitutive heat shock expression responds to modification of Hsp70 copy number in Drosophila melanogaster but does not compensate for loss of thermotolerance in Hsp70 null flies. BMC Biology 6:5PubMedCrossRefGoogle Scholar
  7. Blumensteil JP, Hartl DL, Lozovsky ER (2002) Patterns of insertion and deletion in contrasting chromatin domains. Mol Biol Evol 19:2211–2225Google Scholar
  8. Braastad CD, Hovhannisyan H, van Wijnen AJ, Stein JL, Stein GS (2004) Functional characterization of a human histone gene cluster duplication. Gene 342:35–40PubMedCrossRefGoogle Scholar
  9. Clark AG (1994) Invasion and maintenance of a gene duplication. Proc Natl Acad Sci USA 91:2950–2954PubMedCrossRefGoogle Scholar
  10. Comeron JM (1995) A method for estimating the numbers of synonymous and non-synonymous substitutions per site. J Mol Evol 41:1152–1159PubMedCrossRefGoogle Scholar
  11. Cusack BP, Wolf KH (2007) Not born equal: increased rate asymmetry in relocated and retrotransposed rodent gene duplicates. Mol Biol Evol 24:679–686PubMedCrossRefGoogle Scholar
  12. Don RH, Cox PT, Wainwright BJ, Baker K, Mattick JS (1991) ‘Touchdown’ PCR to circumvent spurious priming during gene amplification. Nucleic Acids Res 19:4008PubMedCrossRefGoogle Scholar
  13. Eichler EE (2001) Recent duplication, domain accretion and dynamic mutation of the human genome. Trends Genet 17:661–669PubMedCrossRefGoogle Scholar
  14. Fan C, Chen Y, Long M (2008) Recurrent tandem gene duplication gave rise to functionally divergent genes in Drosophila. Mol Biol Evol 25:1451–1458PubMedCrossRefGoogle Scholar
  15. Feder ME, Krebs RA (1998) Natural and genetic engineering of thermotolerance in Drosophila melanogaster. Am Zool 38:503–517Google Scholar
  16. Fink AL (1999) Chaperone-mediated protein folding. Physiol Rev 79:425–449PubMedGoogle Scholar
  17. Fiumera AC, Dumont BL, Clark AG (2005) Sperm competitive ability in Drosophila melanogaster associated with variation in male reproductive proteins. Genetics 169:243–257PubMedCrossRefGoogle Scholar
  18. Force A, Lynch M, Pickett FB, Amores A, Yan YL, Postlethwait J (1999) Preservation of duplicate genes by complementary, degenerative mutations. Genetics 151:1531–1545PubMedGoogle Scholar
  19. Gaut BS, Ross-Ibarra J (2008) Selection on major components of angiosperm genomes. Science 320:484–486PubMedCrossRefGoogle Scholar
  20. Gloor GB, Preston CR, Johnson-Schlitz DM, Nassif NA, Phillis RW, Benz WK, Robertson HM, Engels WR (1993) Type I repressors of P element mobility. Genetics 135:81–95PubMedGoogle Scholar
  21. Gray YH (2000) It takes two transposons to tango—transposable-element-mediated chromosomal rearrangements. Trends Genet 16:461–468PubMedCrossRefGoogle Scholar
  22. Gu Z, Steinmetz LM, Gu X, Scharfe C, Davis RW, Li WH (2003) Role of duplicate genes in genetic robustness against null mutations. Nature 421:63–66PubMedCrossRefGoogle Scholar
  23. Hoehfeld J, Jentsch S (1997) GrpE-like regulation of the hsc70 chaperone by the antiapoptotic protein BAG-1. EMBO J 16:6209–6216CrossRefGoogle Scholar
  24. Hudson RR, Kreitman M, Aguadé M (1987) A test of neutral molecular evolution based on nucleotide data. Genetics 116:153–159PubMedGoogle Scholar
  25. Kidwell MG, Lisch DR (2001) Perspective: transposable elements, parasitic DNA, and genome evolution. Evol Int J Org Evol 55:1–24Google Scholar
  26. Kondrashov FA, Kondrashov AS (2006) Role of selection in fixation of gene duplications. J Theor Biol 239:141–151PubMedCrossRefGoogle Scholar
  27. Krebs RA, Bettencourt BR (1999) Evolution of thermotolerance and variation in the heat shock protein, Hsp70. Am Zool 39:910–919Google Scholar
  28. Long M, Langley CH (1993) Natural selection and the origin of jungwei, a chimeric processed functional gene in Drosophila. Science 260:91–95PubMedCrossRefGoogle Scholar
  29. Lynch M (2002) Genomics. Gene duplication and evolution. Science 297:1003–1007CrossRefGoogle Scholar
  30. Lynch M, Conery JS (2000) The evolutionary fate and consequences of duplicate genes. Science 290:1151–1155PubMedCrossRefGoogle Scholar
  31. Lynch M, Conery JS (2003) The origins of genome complexity. Science 302:1401–1404PubMedCrossRefGoogle Scholar
  32. Lynch M, Force A (2000) The probability of duplicate-gene preservation by subfunctionalization. Genetics 154:459–473PubMedGoogle Scholar
  33. Lynch M, O’Hely M, Walsh B, Force A (2001) The probability of preservation of a newly arisen gene duplicate. Genetics 159:1789–1804PubMedGoogle Scholar
  34. Ma J, Devos KM, Bennetzen JL (2004) Analyses of LTR-retrotranposon structures reveal recent and rapid genomic DNA loss in rice. Genome Res 14:860–869PubMedCrossRefGoogle Scholar
  35. McDonald JF (1995) Transposable elements—possible catalysts of organismic evolution. Trends Ecol Evol 10:123–126CrossRefGoogle Scholar
  36. McDonald JH, Kreitman M (1991) Adaptive protein evolution at the Adh locus in Drosophila. Nature 351:652–654PubMedCrossRefGoogle Scholar
  37. Meiklejohn CD, Montooth KL, Rand DM (2007) Positive and negative selection on the mitochondrial genome. Trends Genet 23:259–263PubMedCrossRefGoogle Scholar
  38. Michalak P, Minkov I, Helin A, Lerman DN, Bettencourt BR, Feder ME, Korol AB, Nevo E (2001) Genetic evidence for adaptation-driven incipient speciation of Drosophila melanogaster along a microclimatic contrast in “Evolution Canyon”, Israel. Proc Natl Acad Sci USA 98:13195–13200PubMedCrossRefGoogle Scholar
  39. Nei M (1968) Evolutionary change of linkage intensity. Nature 218:1160–1161PubMedCrossRefGoogle Scholar
  40. Nei M, Gojobori T (1986) Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 3:418–426PubMedGoogle Scholar
  41. Nei M, Li WH (1979) Mathematical model for studying genetic variation in terms of restriction endonucleases. Proc Natl Acad Sci USA 76:5269–5373PubMedCrossRefGoogle Scholar
  42. Nei M, Gu X, Sitnikova T (1997) Evolution by the birth-and-death process in multigene families of the vertebrate immune system. Proc Natl Acad Sci USA 94:7799–7806PubMedCrossRefGoogle Scholar
  43. Nollen EA, Kabakov AE, Brunsting JF, Kanon B, Hohfeld J, Kampinga HH (2001) Modulation of in vivo HSP70 chaperone activity by HIP and Bag-1. J Biol Chem 276:4677–4682PubMedCrossRefGoogle Scholar
  44. Ohno S (1970) Evolution by gene duplication. Springer-Verlag, New YorkGoogle Scholar
  45. Ohta T (1983) On the evolution of multigene families. Theor Popul Biol 23:216–240PubMedCrossRefGoogle Scholar
  46. Petrov DA, Chao YC, Stephenson EC, Hartl DL (1998) Pseudogene evolution in Drosophila suggest high rate of DNA loss. Mol Biol Evol 15:1562–1567PubMedGoogle Scholar
  47. Powell AJ, Conant GC, Brown DE, Carbone I, Dean RA (2008) Altered patterns of gene duplication and differential gene gain and loss in fungal pathogens. BMC Genomics 9:147PubMedCrossRefGoogle Scholar
  48. Prapapanich V, Chen S, Toran EJ, Rimermann RA, Smith DF (1996) Mutational analysis of the hsp70-interacting protein HIP. Mol Cell Biol 16:6200–6207PubMedGoogle Scholar
  49. Pritchard JK, Schaeffer SW (1997) Polymorphism and divergence at the Drosophila pseudogene locus. Genetics 147:199–208PubMedGoogle Scholar
  50. Rako L, Blacket MJ, McKechnie SW, Hoffmann AA (2007) Candidate genes and thermal phenotypes: identifying ecologically important genetic variation for thermotolerance in the Australian Drosophila melanogaster cline. Mol Ecol 16:2948–2957PubMedCrossRefGoogle Scholar
  51. Rand DM, Kann LM (1996) Excess amino acid polymorphism in mitochondrial DNA: contrasts among genes from Drosophila, mice, and human. Mol Biol Evol 13:735–748PubMedGoogle Scholar
  52. Rosato E, Peixoto AA, Barbujani G, Costa R, Kyriacou CP (1994) Molecular polymorphism in the period gene of Drosophila simulans. Genetics 138:693–707PubMedGoogle Scholar
  53. Rouyer F, Rachidi M, Pikielny C, Rosbash M (1997) A new gene encoding a putative transcription factor regulated by the Drosophila circadian clock. EMBO J 13:3944–3954CrossRefGoogle Scholar
  54. Rozas J, Aguade M (1994) Gene conversion is involved in the transfer of genetic information between naturally occurring inversions of Drosophila. Proc Natl Acad Sci USA 91:11517–11521PubMedCrossRefGoogle Scholar
  55. Rozas J, Segarra C, Aguade M (1999) Molecular population genetics of therp49 gene region in different chromosomal inversion of Drosophila subobscura. Genetics 151:189–202PubMedGoogle Scholar
  56. Rubin GM, Yandell MD, Wortman JR, Gabor Miklos GL, Nelson CR, Hariharan IK, Fortini ME, Li PW, Apweiler R, Fleischmann W, Cherry JM, Henikoff S, Skupski MP, Misra S, Ashburner M, Birney E, Boguski MS, Brody T, Brokstein P, Celniker SE, Chervitz SA, Coates D, Cravchik A, Gabrielian A, Galle RF, Gelbart WM, George RA, Goldstein LS, Gong F, Guan P, Harris NL, Hay BA, Hoskins RA, Li J, Li Z, Hynes RO, Jones SJ, Kuehl PM, Lemaitre B, Littleton JT, Morrison DK, Mungall C, O’Farrell PH, Pickeral OK, Shue C, Vosshall LB, Zhang J, Zhao Q, Zheng XH, Lewis S (2000) Comparitive genomics of the eukaryotes. Science 287:2204–2215PubMedCrossRefGoogle Scholar
  57. Russo CA, Takesaki N, Nei M (1995) Molecular phyplogeny and divergence times of drosophilid species. Mol Biol Evol 12:391–404PubMedGoogle Scholar
  58. Schulenburg H, Boehnisch C (2008) Diversification and adaptive sequence evolution of Caenorhabditis lysozymes (Nematoda: Rhabditidae). BMC Evol Biol 8:114PubMedCrossRefGoogle Scholar
  59. Smith DF (1998) Sequence motifs shared between chaperone components participating in the assembly of progesterone receptor complexes. Biol Chem 379:283–288PubMedCrossRefGoogle Scholar
  60. Tajima F (1989) Statistical method for testing the neutral mutation hypothesis by DNA polymorphism. Genetics 123:585–595PubMedGoogle Scholar
  61. Temperley ND, Berlin S, Paton IR, Griffin DK, Burt DW (2008) Evolution of the chicken Toll-like receptor gene family: a story of gene gain and gene loss. BMC Genomics 9:62PubMedCrossRefGoogle Scholar
  62. Teshima KM, Innan H (2004) The effects of gene conversion on the divergence between duplicated genes. Genetics 166:1553–1560PubMedCrossRefGoogle Scholar
  63. Teshima KM, Innan H (2008) Neofunctionalization of duplicated genes under the pressure of gene conversion. Genetics 178:1385–1398PubMedCrossRefGoogle Scholar
  64. Thornton K, Long M (2002) Rapid divergence of gene duplicates on the Drosophila melanogaster X chromosome. Mol Biol Evol 19:918–925PubMedGoogle Scholar
  65. Velten M, Villoutreix BO, Ladjimi MM (2000) Quaternary structure of the HSC70 cochaperone HIP. Biochemistry 39:307–315PubMedCrossRefGoogle Scholar
  66. Velten M, Gomez-Vrielunck N, Chaffotte A, Ladjimi MM (2002) Domain structure of the HSC70 cochaperone, HIP. J Biol Chem 277:259–266PubMedCrossRefGoogle Scholar
  67. Wagner A (1998) The fate of duplicated genes: Loss or new function? Bioessays 20:785–788PubMedCrossRefGoogle Scholar
  68. Walsh JB (1995) How often do duplicated genes evolve new fuctions? Genetics 139:421–428PubMedGoogle Scholar
  69. Wang W, Brunet FG, Nevo E, Long M (2002) Origin of sphinx, a young chimeric RNA gene in Drosophila melanogaster. Proc Natl Acad Sci USA 99:4448–4453PubMedCrossRefGoogle Scholar
  70. Watterson GA (1975) On the number of segregating sites in genetical models without recombination. Theor Popul Biol 7:256–276PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Biological SciencesUniversity of Massachusetts LowellLowellUSA
  2. 2.Network BiosystemsWoburnUSA

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