Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Turning a hobby into a job: How duplicated genes find new functions

Nature Reviews Genetics volume 9, pages 938–950 (2008)Cite this article

Key Points

  • Natural selection uses duplicated genes as raw material for functional innovation, co-opting their existing features to new functions.

  • Understanding genetic innovation requires two questions to be addressed: which gene was involved in the duplication; and how has natural selection acted on that duplication to optimize the novel function?

  • Genes with functions such as enzymes, transporters and transcription factors often survive in duplicate. However, the mechanism of duplication is important: genes that are part of complex cellular networks are more easily duplicated by whole-genome duplication (WGD) than by small-scale duplication (SSD).

  • In order to have the potential to acquire a new function, a duplicate gene must come under the protection of natural selection so that it is not eliminated by degenerative mutations. At least three mechanisms can allow natural selection to preserve a duplicate gene pair: neofunctionalization, subfunctionalization and selection for gene dosage.

  • Strikingly, all three of the above mechanisms have been involved in the appearance of novel functions. For instance, dosage selection can maintain a gene duplication in order to provide sufficient expression of a gene product with a weak but beneficial new activity.

  • Such existing minor activities in genes might or might not be related to the gene's evolved function. Examples include enzymes with minor activities for substrates related to their primary substrate, and receptors with affinities for several ligands.

  • Subfunctionalization can also be involved in the process of generating novelty. An example is the GAL1–GAL3 gene duplication in Saccharomyces cerevisiae, in which a single gene first gained a novel function that was then optimized by duplication and adaptive subfunctionalization.

Abstract

Gene duplication provides raw material for functional innovation. Recent advances have shed light on two fundamental questions regarding gene duplication: which genes tend to undergo duplication? And how does natural selection subsequently act on them? Genomic data suggest that different gene classes tend to be retained after single-gene and whole-genome duplications. We also know that functional differences between duplicate genes can originate in several different ways, including mutations that directly impart new functions, subdivision of ancestral functions and selection for changes in gene dosage. Interestingly, in many cases the 'new' function of one copy is a secondary property that was always present, but that has been co-opted to a primary role after the duplication.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Potential fates of duplicate genes.
Figure 2: Hypothetical example of network evolution following a genome duplication.
Figure 3: The isoleucine and valine biosynthetic pathways in Saccharomyces cerevisiae.
Figure 4: Divergence of the aldosterone and cortisol receptors in tetrapods.
Figure 5: Subfunctionalization of a galactose catabolism gene regulatory circuit in Saccharomyces cerevisiae.

References

  1. Darwin, C. The Origin of Species by Means of Natural Selection (John Murry, London, 1859).

    Google Scholar 

  2. Ruse, M. Is evolution a secular religion? Science 299, 1523–1524 (2003).

    Article  CAS  PubMed  Google Scholar 

  3. Müller, G. B. & Wagner, G. P. Novelty in evolution: restructuring the concept. Annu. Rev. Ecol. Syst. 22, 229–256 (1991).

    Article  Google Scholar 

  4. Gould, S. J. in The Panda's Thumb 19–26 (W. W. Norton, New York, 1980).

    Google Scholar 

  5. Gould, S. J. & Vrba, E. S. Exaptation — a missing term in the science of form. Paleobiology 8, 4–15 (1982).

    Article  Google Scholar 

  6. Ji, Q., Norell, M. A., Gao, K.-Q., Ji, S.-A. & Ren, D. The distribution of integumentary structures in a feathered dinosaur. Nature 410, 1084–1088 (2001).

    Article  CAS  PubMed  Google Scholar 

  7. Xu, X., Zhou, Z.-H. & Prum, R. O. Branched integumental structures in Sinornithosaurus and the origin of feathers. Nature 410, 200–204 (2001).

    Article  CAS  PubMed  Google Scholar 

  8. Shubin, N., Tabin, C. & Carroll, S. Fossils, genes and the evolution of animal limbs. Nature 388, 639–648 (1997).

    Article  CAS  PubMed  Google Scholar 

  9. Taylor, J. S. & Raes, J. Duplication and divergence: the evolution of new genes and old ideas. Annu. Rev. Genet. 38, 615–643 (2004).

    Article  CAS  PubMed  Google Scholar 

  10. Ohno, S. Evolution by Gene Duplication (Springer, New York, 1970).

    Book  Google Scholar 

  11. Lynch, M. The frailty of adaptive hypotheses for the origins of organismal complexity. Proc. Natl Acad. Sci. USA 104 (Suppl. 1), 8597–8604 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Lynch, M. & Conery, J. S. The evolutionary fate and consequences of duplicate genes. Science 290, 1151–1155 (2000). A landmark paper that was the first to estimate genome-wide rates of formation and death of duplicated genes in eukaryotes, and the first to demonstrate the relaxation of selective constraints on duplicated genes.

    Article  CAS  PubMed  Google Scholar 

  13. Davis, J. C. & Petrov, D. A. Preferential duplication of conserved proteins in eukaryotic genomes. PLoS Biol. 2, E55 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Li, L., Huang, Y., Xia, X. & Sun, Z. Preferential duplication in the sparse part of yeast protein interaction network. Mol. Biol. Evol. 23, 2467–2473 (2006).

    Article  CAS  PubMed  Google Scholar 

  15. He, X. & Zhang, J. Higher duplicability of less important genes in yeast genomes. Mol. Biol. Evol. 23, 144–151 (2006).

    Article  CAS  PubMed  Google Scholar 

  16. Deluna, A. et al. Exposing the fitness contribution of duplicated genes. Nature Genet. 40, 676–681 (2008).

    Article  CAS  PubMed  Google Scholar 

  17. Drummond, D. A., Raval, A. & Wilke, C. O. A single determinant dominates the rate of yeast protein evolution. Mol. Biol. Evol. 23, 327–337 (2006). The authors demonstrate that the rate of translation of mRNA is the major determinant of nonsynonymous and synonymous evolutionary rates in yeasts.

    Article  CAS  PubMed  Google Scholar 

  18. Paterson, A. H. et al. Many gene and domain families have convergent fates following independent whole-genome duplication events in Arabidopsis, Oryza, Saccharomyces and Tetraodon. Trends Genet. 22, 597–602 (2006).

    Article  CAS  PubMed  Google Scholar 

  19. Papp, B., Pal, C. & Hurst, L. D. Dosage sensitivity and the evolution of gene families in yeast. Nature 424, 194–197 (2003).

    Article  CAS  PubMed  Google Scholar 

  20. Wapinski, I., Pfeffer, A., Friedman, N. & Regev, A. Natural history and evolutionary principles of gene duplication in fungi. Nature 449, 54–61 (2007).

    Article  CAS  PubMed  Google Scholar 

  21. Aury, J. M. et al. Global trends of whole-genome duplications revealed by the ciliate Paramecium tetraurelia. Nature 444, 171–178 (2006).

    Article  CAS  PubMed  Google Scholar 

  22. Seoighe, C. & Wolfe, K. H. Yeast genome evolution in the post-genome era. Curr. Opin. Microbiol. 2, 548–554 (1999).

    Article  CAS  PubMed  Google Scholar 

  23. Blanc, G. & Wolfe, K. H. Functional divergence of duplicated genes formed by polyploidy during Arabidopsis evolution. Plant Cell 16, 1679–1691 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Harbison, C. T. et al. Transcriptional regulatory code of a eukaryotic genome. Nature 431, 99–104 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Maere, S. et al. Modeling gene and genome duplications in eukaryotes. Proc. Natl Acad. Sci. USA 102, 5454–5459 (2005). The first application of mathematical modelling techniques to study variation in the propensities of different functional classes of genes to survive in duplicate after WGD or SSD events.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Guan, Y., Dunham, M. J. & Troyanskaya, O. G. Functional analysis of gene duplications in Saccharomyces cerevisiae. Genetics 175, 933–943 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hakes, L., Pinney, J. W., Lovell, S. C., Oliver, S. G. & Robertson, D. L. All duplicates are not equal: the difference between small-scale and genome duplication. Genome Biol. 8, R209 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Scannell, D. R. et al. Independent sorting-out of thousands of duplicated gene pairs in two yeast species descended from a whole-genome duplication. Proc. Natl Acad. Sci. USA 104, 8397–8402 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Conant, G. C. & Wolfe, K. H. Increased glycolytic flux as an outcome of whole-genome duplication in yeast. Mol. Syst. Biol. 3, 129 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Freeling, M. & Thomas, B. C. Gene-balanced duplications, like tetraploidy, provide predictable drive to increase morphological complexity. Genome Res. 16, 805–814 (2006).

    Article  CAS  PubMed  Google Scholar 

  31. Dean, E. J., Davis, J. C., Davis, R. W. & Petrov, D. A. Pervasive and persistent redundancy among duplicated genes in yeast. PLoS Genet. 4, e1000113 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Musso, G., Zhang, Z. & Emili, A. Retention of protein complex membership by ancient duplicated gene products in budding yeast. Trends Genet. 23, 266–269 (2007).

    Article  CAS  PubMed  Google Scholar 

  33. Byrne, K. P. & Wolfe, K. H. Consistent patterns of rate asymmetry and gene loss indicate widespread neofunctionalization of yeast genes after whole-genome duplication. Genetics 175, 1341–1350 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Piškur, J., Rozpedowska, E., Polakova, S., Merico, A. & Compagno, C. How did Saccharomyces evolve to become a good brewer? Trends Genet. 22, 183–186 (2006).

    Article  CAS  PubMed  Google Scholar 

  35. Thomson, J. M. et al. Resurrecting ancestral alcohol dehydrogenases from yeast. Nature Genet. 37, 630–635 (2005).

    Article  CAS  PubMed  Google Scholar 

  36. Zhang, J., Zhang, Y. P. & Rosenberg, H. F. Adaptive evolution of a duplicated pancreatic ribonuclease gene in a leaf-eating monkey. Nature Genet. 30, 411–415 (2002).

    Article  CAS  PubMed  Google Scholar 

  37. Piatigorsky, J. et al. Gene sharing by delta-crystallin and argininosuccinate lyase. Proc. Natl Acad. Sci. USA 85, 3479–3483 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Wistow, G. & Piatigorsky, J. Recruitment of enzymes as lens structural proteins. Science 236, 1554–1556 (1987).

    Article  CAS  PubMed  Google Scholar 

  39. Chen, L., DeVries, A. L. & Cheng, C. H. Evolution of antifreeze glycoprotein gene from a trypsinogen gene in Antarctic notothenioid fish. Proc. Natl Acad. Sci. USA 94, 3811–3816 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Smith, A. A. et al. Gene duplication and separation of functions in alphaB-crystallin from zebrafish (Danio rerio). FEBS J. 273, 481–490 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Williford, A., Stay, B. & Bhattacharya, D. Evolution of a novel function: nutritive milk in the viviparous cockroach, Diploptera punctata. Evol. Dev. 6, 67–77 (2004).

    Article  CAS  PubMed  Google Scholar 

  42. Korchi, A., Brossut, R., Bouhin, H. & Delachambre, J. cDNA cloning of an adult male putative lipocalin specific to tergal gland aphrodisiac secretion in an insect (Leucophaea maderae). FEBS Lett. 449, 125–128 (1999).

    Article  CAS  PubMed  Google Scholar 

  43. Lynch, M. & Conery, J. S. The origins of genome complexity. Science 302, 1401–1404 (2003).

    Article  CAS  PubMed  Google Scholar 

  44. Wagner, A. Energy constraints on the evolution of gene expression. Mol. Biol. Evol. 22, 1365–1374 (2005).

    Article  CAS  PubMed  Google Scholar 

  45. Bergthorsson, U., Andersson, D. I. & Roth, J. R. Ohno's dilemma: evolution of new genes under continuous selection. Proc. Natl Acad. Sci. USA 104, 17004–17009 (2007). The authors propose the IAD model of co-option of minor activities of genes.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Gerstein, A. C., Chun, H.-J., Grant, A. & Otto, S. P. Genomic convergence toward diploidy in Saccharomyces cerevisiae. PLoS Genet. 2, e145 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Li, W.-H. Rate of gene silencing at duplicate loci: a theoretical study and interpretation of data from tetraploid fish. Genetics 95, 237–258 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Nei, M. & Roychoudhury, A. K. Probability of fixation of nonfunctional genes at duplicate loci. Am. Nat. 107, 362–372 (1973).

    Article  Google Scholar 

  49. Force, A. et al. Preservation of duplicate genes by complementary, degenerative mutations. Genetics 151, 1531–1545 (1999). The paper that introduced the terms subfunctionalization and neofunctionalization, and that proposed that a specific form of subfunctionalization (DDC) is a frequent cause of the initial preservation of duplicated genes in eukaryotes.

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Hughes, A. L. The evolution of functionally novel proteins after gene duplication. Proc. Roy. Soc. Lond. B 256, 119–124 (1994).

    Article  CAS  Google Scholar 

  51. Kimura, M. & Ohta, T. On some principles governing molecular evolution. Proc. Natl Acad. Sci. USA 71, 2848–2852 (1974).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Plaitakis, A., Spanaki, C., Mastorodemos, V. & Zaganas, I. Study of structure–function relationships in human glutamate dehydrogenases reveals novel molecular mechanisms for the regulation of the nerve tissue-specific (GLUD2) isoenzyme. Neurochem. Int. 43, 401–410 (2003).

    Article  CAS  PubMed  Google Scholar 

  53. Burki, F. & Kaessmann, H. Birth and adaptive evolution of a hominoid gene that supports high neurotransmitter flux. Nature Genet. 36, 1061–1063 (2004).

    Article  CAS  PubMed  Google Scholar 

  54. Shashidharan, P. et al. Novel human glutamate dehydrogenase expressed in neural and testicular tissues and encoded by an X-linked intronless gene. J. Biol. Chem. 269, 16971–16976 (1994).

    CAS  PubMed  Google Scholar 

  55. Zhang, J., Dean, A. M., Brunet, F. & Long, M. Evolving protein functional diversity in new genes of Drosophila. Proc. Natl Acad. Sci. USA 101, 16246–16250 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Corbin, C. J. et al. Paralogues of porcine aromatase cytochrome P450: a novel hydroxylase activity is associated with the survival of a duplicated gene. Endocrinology 145, 2157–2164 (2004).

    Article  CAS  PubMed  Google Scholar 

  57. Stoltzfus, A. On the possibility of constructive neutral evolution. J. Mol. Evol. 49, 169–181 (1999).

    Article  CAS  PubMed  Google Scholar 

  58. van Hoof, A. Conserved functions of yeast genes support the duplication, degeneration and complementation model for gene duplication. Genetics 171, 1455–1461 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Hittinger, C. T. & Carroll, S. B. Gene duplication and the adaptive evolution of a classic genetic switch. Nature 449, 677–681 (2007).

    Article  CAS  PubMed  Google Scholar 

  60. Hughes, A. L. Gene duplication and the origin of novel proteins. Proc. Natl Acad. Sci. USA 102, 8791–8792 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Des Marais, D. L. & Rausher, M. D. Escape from adaptive conflict after duplication in an anthocyanin pathway gene. Nature 454, 762–765 (2008).

    Article  CAS  PubMed  Google Scholar 

  62. Cusack, B. P. & Wolfe, K. H. When gene marriages don't work out: divorce by subfunctionalization. Trends Genet. 23, 270–272 (2007).

    Article  CAS  PubMed  Google Scholar 

  63. Blanchard, J. L. & Lynch, M. Organellar genes: why do they end up in the nucleus? Trends Genet. 16, 315–320 (2000).

    Article  CAS  PubMed  Google Scholar 

  64. Teichmann, S. & Babu, M. M. Gene regulatory network growth by duplication. Nature Genet. 36, 492–496 (2004).

    Article  CAS  PubMed  Google Scholar 

  65. Berg, J., Lässig, M. & Wagner, A. Structure and evolution of protein interaction networks: a statistical model for link dynamics and gene duplications. BMC Evol. Biol. 4, 51 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Chung, F., Lu, L., Dewey, T. G. & Galas, D. J. Duplication models for biological networks. J. Comput. Biol. 10, 677–687 (2003).

    Article  CAS  PubMed  Google Scholar 

  67. Wagner, A. How the global structure of protein interaction networks evolves. Proc. Roy. Soc. Lond. B 270, 457–466 (2003).

    Article  CAS  Google Scholar 

  68. Pastor-Satorras, R., Smith, E. & Sole, R. V. Evolving protein interaction networks through gene duplication. J. Theor. Biol. 222, 199–210 (2003).

    Article  CAS  PubMed  Google Scholar 

  69. Conant, G. C. & Wolfe, K. H. Functional partitioning of yeast co-expression networks after genome duplication. PLoS Biol. 4, e109 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Kondrashov, F. A. & Kondrashov, A. S. Role of selection in fixation of gene duplications. J. Theor. Biol. 239, 141–151 (2006).

    Article  CAS  PubMed  Google Scholar 

  71. Kondrashov, F. A., Rogozin, I. B., Wolf, Y. I. & Koonin, E. V. Selection in the evolution of gene duplications. Genome Biol. 3, 0008.1–0008.9 (2002).

    Article  Google Scholar 

  72. Price, R. N. et al. Mefloquine resistance in Plasmodium falciparum and increased pfmdr1 gene copy number. Lancet 364, 438–447 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Gonzalez, E. et al. The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science 307, 1434–1440 (2005).

    Article  CAS  PubMed  Google Scholar 

  74. Guillemaud, T. et al. Quantitative variation and selection of esterase gene amplification in Culex pipiens. Heredity 83 (Pt 1), 87–99 (1999).

    Article  CAS  PubMed  Google Scholar 

  75. Riehle, M. M., Bennett, A. F. & Long, A. D. Genetic architecture of thermal adaptation in Escherichia coli. Proc. Natl Acad. Sci. USA 98, 525–530 (2001).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Brown, C. J., Todd, K. M. & Rosenzweig, R. F. Multiple duplications of yeast hexose-transport genes in response to selection in a glucose-limited environment. Mol. Biol. Evol. 15, 931–942 (1998).

    Article  CAS  PubMed  Google Scholar 

  77. Sonti, R. V. & Roth, J. R. Role of gene duplications in the adaptation of Salmonella typhimurium to growth on limiting carbon sources. Genetics 123, 19–28 (1989).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Jensen, R. A. Enzyme recruitment in evolution of new function. Annu. Rev. Microbiol. 30, 409–425 (1976).

    Article  CAS  PubMed  Google Scholar 

  79. Voet, D. & Voet, J. G. Biochemistry (John Wiley & Sons, Inc., Hoboken, New Jersey, 2004).

    Google Scholar 

  80. Gancedo, C. & Flores, C. L. Moonlighting proteins in yeasts. Microbiol. Mol. Biol. Rev. 72, 197–210 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. James, L. C. & Tawfik, D. S. Conformational diversity and protein evolution — a 60-year-old hypothesis revisited. Trends Biochem. Sci. 28, 361–368 (2003).

    Article  CAS  PubMed  Google Scholar 

  82. Copley, S. D. Enzymes with extra talents: moonlighting functions and catalytic promiscuity. Curr. Opin. Chem. Biol. 7, 265–272 (2003).

    Article  CAS  PubMed  Google Scholar 

  83. O'Brien, P. J. & Herschlag, D. Catalytic promiscuity and the evolution of new enzymatic activities. Chem. Biol. 6, R91–R105 (1999).

    Article  CAS  PubMed  Google Scholar 

  84. Yang, K. & Metcalf, W. W. A new activity for an old enzyme: Escherichia coli bacterial alkaline phosphatase is a phosphite-dependent hydrogenase. Proc. Natl Acad. Sci. USA 101, 7919–7924 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. James, L. C., Roversi, P. & Tawfik, D. S. Antibody multispecificity mediated by conformational diversity. Science 299, 1362–1367 (2003). The authors describe an antibody that not only binds distinct antigens (a small aromatic compound and a protein) but seems to do so as the result of possessing at least two distinct free-state structural conformations.

    Article  CAS  PubMed  Google Scholar 

  86. Miller, B. G. & Raines, R. T. Identifying latent enzyme activities: substrate ambiguity within modern bacterial sugar kinases. Biochemistry 43, 6387–6392 (2004).

    Article  CAS  PubMed  Google Scholar 

  87. Miller, B. G. & Raines, R. T. Reconstitution of a defunct glycolytic pathway via recruitment of ambiguous sugar kinases. Biochemistry 44, 10776–10783 (2005).

    Article  CAS  PubMed  Google Scholar 

  88. Hendrickson, H., Slechta, E. S., Bergthorsson, U., Andersson, D. I. & Roth, J. R. Amplification-mutagenesis: evidence that 'directed' adaptive mutation and general hypermutability result from growth with a selected gene amplification. Proc. Natl Acad. Sci. USA 99, 2164–2169 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Roth, J. R. & Andersson, D. I. Adaptive mutation: how growth under selection stimulates Lac(+) reversion by increasing target copy number. J. Bacteriol. 186, 4855–4860 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Francino, M. P. An adaptive radiation model for the origin of new gene functions. Nature Genet. 37, 573–577 (2005).

    Article  CAS  PubMed  Google Scholar 

  91. Lynch, M. & Force, A. The probability of duplicate gene preservation by subfunctionalization. Genetics 154, 459–473 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  92. He, X. & Zhang, J. Rapid subfunctionalization accompanied by prolonged and substantial neofunctionalization in duplicate gene evolution. Genetics 169, 1157–1164 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  93. Rastogi, S. & Liberles, D. A. Subfunctionalization of duplicated genes as a transition state to neofunctionalization. BMC Evol. Biol. 5, 28 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Thornton, J. W., Need, E. & Crews, D. Resurrecting the ancestral steroid receptor: ancient origin of estrogen signaling. Science 301, 1714–1717 (2003).

    CAS  PubMed  Google Scholar 

  95. Thornton, J. W. Evolution of vertebrate steroid receptors from an ancestral estrogen receptor by ligand exploitation and serial genome expansions. Proc. Natl Acad. Sci. USA 98, 5671–5676 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Bridgham, J. T., Carroll, S. M. & Thornton, J. W. Evolution of hormone-receptor complexity by molecular exploitation. Science 312, 97–101 (2006).

    Article  CAS  PubMed  Google Scholar 

  97. Farman, N. & Rafestin-Oblin, M. E. Multiple aspects of mineralocorticoid selectivity. Am. J. Physiol. Renal Physiol. 280, F181–F192 (2001).

    Article  CAS  PubMed  Google Scholar 

  98. Gronemeyer, H., Gustafsson, J. A. & Laudet, V. Principles for modulation of the nuclear receptor superfamily. Nature Rev. Drug Discov. 3, 950–964 (2004).

    Article  CAS  Google Scholar 

  99. Bülow, H. E. & Bernhardt, R. Analyses of the CYP11B gene family in the guinea pig suggest the existence of a primordial CYP11B gene with aldosterone synthase activity. Eur. J. Biochem. 269, 3838–3846 (2002).

    Article  CAS  PubMed  Google Scholar 

  100. Bhat, P. J. & Murthy, T. V. Transcriptional control of the GAL/MEL regulon of yeast Saccharomyces cerevisiae: mechanism of galactose-mediated signal transduction. Mol. Microbiol. 40, 1059–1066 (2001).

    Article  CAS  PubMed  Google Scholar 

  101. Zenke, F. T. et al. Activation of Gal4p by galactose-dependent interaction of galactokinase and Gal80p. Science 272, 1662–1665 (1996).

    Article  CAS  PubMed  Google Scholar 

  102. Warda, M. & Han, J. Retracted: Mitochondria, the missing link between body and soul: proteomic prospective evidence. Proteomics 8, I–XXIII (2008).

    Article  Google Scholar 

  103. Shiu, S. H., Byrnes, J. K., Pan, R., Zhang, P. & Li, W. H. Role of positive selection in the retention of duplicate genes in mammalian genomes. Proc. Natl Acad. Sci. USA 103, 2232–2236 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Nielsen, R. et al. A scan for positively selected genes in the genomes of humans and chimpanzees. PLoS Biol. 3, e170 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Marques, A. C., Dupanloup, I., Vinckenbosch, N., Reymond, A. & Kaessmann, H. Emergence of young human genes after a burst of retroposition in primates. PLoS Biol. 3, e357 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Kreitman, M. & Akashi, H. Molecular evidence for natural selection. Annu. Rev. Ecol. Syst. 26, 403–422 (1995).

    Article  Google Scholar 

  107. Yang, Z. Maximum likelihood estimation on large phylogenies and analysis of adaptive evolution in human influenza virus A. J. Mol. Evol. 51, 423–432 (2000).

    Article  CAS  PubMed  Google Scholar 

  108. Zhang, J. Z., Rosenberg, H. F. & Nei, M. Positive Darwinian selection after gene duplication in primate ribonuclease genes. Proc. Natl Acad. Sci. USA 95, 3708–3713 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Sharp, P. M. In search of molecular darwinism. Nature 385, 111–112 (1997).

    PubMed  Google Scholar 

  110. Chain, F. J. & Evans, B. J. Multiple mechanisms promote the retained expression of gene duplicates in the tetraploid frog Xenopus laevis. PLoS Genet. 2, e56 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Cairns, J., Overbaugh, J. & Miller, S. The origin of mutants. Nature 335, 142–145 (1988).

    Article  CAS  PubMed  Google Scholar 

  112. Cairns, J. & Foster, P. L. Adaptive reversion of a frameshift mutation in Escherichia coli. Genetics 128, 695–701 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Andersson, D. I., Slechta, E. S. & Roth, J. R. Evidence that gene amplification underlies adaptive mutability of the bacterial lac operon. Science 282, 1133–1135 (1998).

    Article  CAS  PubMed  Google Scholar 

  114. Kugelberg, E., Kofoid, E., Reams, A. B., Andersson, D. I. & Roth, J. R. Multiple pathways of selected gene amplification during adaptive mutation. Proc. Natl Acad. Sci. USA 103, 17319–17324 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Romero, D. & Palacios, R. Gene amplification and genomic plasticity in prokaryotes. Annu. Rev. Genet. 31, 91–111 (1997).

    Article  CAS  PubMed  Google Scholar 

  116. Byrne, K. P. & Wolfe, K. H. The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res. 15, 1456–1461 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Cherry, J. M. et al. SGD: Saccharomyces Genome Database. Nucleic Acids Res. 26, 73–80 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank K. Byrne, B. Cusack, J. Gordon, N. Khaldi, and J. Mower for discussions regarding the fates of duplicated genes. We would also like to thank three anonymous reviewers for critical comments. This work was supported by Science Foundation Ireland.

Author information

Authors and Affiliations

  1. Division of Animal Sciences, University of Missouri–Columbia, 163B Animal Sciences Center, 920 East Campus Drive, Columbia, 65211-5300, Missouri, USA

    Gavin C. Conant

  2. Smurfit Institute of Genetics, University of Dublin, Trinity College, Dublin, 2, Ireland

    Kenneth H. Wolfe

Authors
  1. Gavin C. Conant
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kenneth H. Wolfe
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kenneth H. Wolfe.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Gavin C. Conant's homepage

Wolfe Laboratory homepage

PubCrawler

Glossary

Subfunctionalization

A pair of duplicate genes are said to be subfunctionalized if each of the two copies of the gene performs only a subset of the functions of the ancestral single copy gene.

Genetic drift

Random fluctuations through time in the allele frequencies of a population, caused by a sampling effect in small populations. Drift can overcome the effects of natural selection if the selective differences between alleles are small.

Neofunctionalization

A pair of duplicate genes in a population are said to be neofunctionalized if one of the two genes possesses a new, selectively beneficial function that was absent in the population before the duplication.

Retrotransposed

Describes a gene that has undergone duplication through a process that involves an mRNA intermediate. It occurs when a reverse transcriptase enzyme synthesizes DNA from an mRNA template and the DNA is then integrated into the genome. Because retrotransposition usually uses mature mRNAs as a substrate, the resulting duplicate genes often lack introns.

Degree distribution

The degree of a node in a network (in this case, a gene) is the number of interactions it has with other nodes in the network. Thus, in a protein–protein interaction network, the degree of a gene is the number of proteins that the product of the gene interacts with. The degree distribution of a network describes the frequency of nodes in that network with a given degree: many networks of biological interest show a power-law degree distribution.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Conant, G., Wolfe, K. Turning a hobby into a job: How duplicated genes find new functions. Nat Rev Genet 9, 938–950 (2008). https://doi.org/10.1038/nrg2482

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrg2482

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing