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New genes as drivers of phenotypic evolution

Nature Reviews Genetics volume 14, pages 645–660 (2013)Cite this article

Subjects

A Corrigendum to this article was published on 22 August 2013

This article has been updated

Key Points

  • The study of phenotypic evolution is of central importance for understanding the evolution of biological diversity.

  • The contribution of new genes to the genetic circuitry underlying the phenotypic evolution of various species, particularly mammals and Drosophila spp., has attracted considerable research interest.

  • An important theme to emerge is that many new genes have evolved indispensable roles in fundamental biological processes, including development, reproduction, brain function and behaviour.

  • The process of gene evolution is so rapid that the examined species have already added species-specific or lineage-specific essential genes to the genetic systems that govern these biological processes.

  • The molecular explanations for how new genes integrate into existing networks and become essential components are currently under investigation.

  • These observations revealed previously unexpected genetic diversity that drove the evolution of phenotypes, and they raised new interesting problems to tackle in the field of genetics and evolution.

Abstract

During the course of evolution, genomes acquire novel genetic elements as sources of functional and phenotypic diversity, including new genes that originated in recent evolution. In the past few years, substantial progress has been made in understanding the evolution and phenotypic effects of new genes. In particular, an emerging picture is that new genes, despite being present in the genomes of only a subset of species, can rapidly evolve indispensable roles in fundamental biological processes, including development, reproduction, brain function and behaviour. The molecular underpinnings of how new genes can develop these roles are starting to be characterized. These recent discoveries yield fresh insights into our broad understanding of biological diversity at refined resolution.

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Figure 1: Several new genes evolved novel biochemical functions.
Figure 2: New genes participate in developmental processes in Drosophila spp.
Figure 3: The involvement of new genes in the development of Drosophila spp., and in the brains of Drosophila spp. and humans.
Figure 4: The functions of the young nsr gene in sperm development in Drosophila spp.
Figure 5: The rapid and extensive evolution of gene expression networks by integration of the new gene Zeus in Drosophila spp.

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Change history

  • 22 August 2013

    On page 655 of the above article, the sentence starting "Indeed, for male-expressed genes..." was corrected to state that X→A gene traffic by DNA-based duplication has been detected in Drosophila spp. and Teleopsis spp. Also on page 655, the sentence starting "Strikingly, transcriptome analyses of the human brain..." was corrected to state that the region of the human brain which showed enriched expression for new genes was the prefrontal cortex. On page 656, in the opening paragraph of the Evolution of essential functions subsection, the text was adjusted to clarify that neofunctionalization is also a possible route to new gene essentiality and that the findings of reference 46 are consistent with a process of neofunctionalization rather than subfunctionalization. Finally, in Table 1, the reference was corrected for the Pros28.1A gene. The article has been corrected online. The authors apologize for these errors.

References

  1. Long, M., Betran, E., Thornton, K. & Wang, W. The origin of new genes: glimpses from the young and old. Nature Rev. Genet. 4, 865–875 (2003).

    Article  CAS  PubMed  Google Scholar 

  2. Kaessmann, H. Origins, evolution, and phenotypic impact of new genes. Genome Res. 20, 1313–1326 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Ding, Y., Zhou, Q. & Wang, W. Origins of new genes and evolution of their novel functions. Annu. Rev. Ecol. Evol. Syst. 43, 345–363 (2012).

    Article  Google Scholar 

  4. Long, M., VanKuren, N. W., Chen, S. & Vibranovski, M. D. New gene evolution: little did we know. Annu. Rev. Genet. (in the press).

  5. Hardison, R. C. Evolution of hemoglobin and its genes. Cold Spring Harb. Perspect. Med. 2, a011627 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Xiong, J., Fischer, W. M., Inoue, K., Nakahara, M. & Bauer, C. E. Molecular evidence for the early evolution of photosynthesis. Science 289, 1724–1730 (2000).

    Article  CAS  PubMed  Google Scholar 

  7. Long, M. & Langley, C. H. Natural selection and the origin of jingwei, a chimeric processed functional gene in Drosophila. Science 260, 91–95 (1993).

    Article  CAS  PubMed  Google Scholar 

  8. Kaessmann, H., Vinckenbosch, N. & Long, M. RNA-based gene duplication: mechanistic and evolutionary insights. Nature Rev. Genet. 10, 19–31 (2009).

    Article  CAS  PubMed  Google Scholar 

  9. Tautz, D. & Domazet-Lošo, T. The evolutionary origin of orphan genes. Nature Rev. Genet. 12, 692–702 (2011).

    Article  CAS  PubMed  Google Scholar 

  10. Ding, Y. et al. A young Drosophila duplicate gene plays essential roles in spermatogenesis by regulating several Y-linked male fertility genes. PLoS Genet. 6, e1001255 (2010). This functional analysis of a new gene in D. melanogaster reveals the rapid evolution of an essential role in spermatogenesis.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Zhang, Y. E., Landback, P., Vibranovski, M. D. & Long, M. Accelerated recruitment of new brain development genes into the human genome. PLoS Biol. 9, e1001179 (2011). This reports that an enhanced rate of new-gene origination underlies brain development in humans and other primates.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Krebs, J. E., Goldstein, E. S. & Kilpatrick, S. T. Lewin's Essential Genes (Jones & Bartlett Publishers, 2009).

    Google Scholar 

  13. Perrimon, N., Ni, J.-Q. & Perkins, L. In vivo RNAi: today and tomorrow. Cold Spring Harb. Perspect. Biol. 2, a003640 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Venken, K. J. T. & Bellen, H. J. Emerging technologies for gene manipulation in Drosophila melanogaster. Nature Rev. Genet. 6, 167–178 (2005).

    Article  PubMed  Google Scholar 

  15. Ohno, S. Evolution by Gene Duplication (George Alien & Unwin Ltd, 1970).

    Book  Google Scholar 

  16. Wang, W., Zhang, J., Alvarez, C., Llopart, A. & Long, M. The origin of the Jingwei gene and the complex modular structure of its parental gene, Yellow Emperor, in Drosophila melanogaster. Mol. Biol. Evol. 17, 1294–1301 (2000).

    Article  CAS  PubMed  Google Scholar 

  17. 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 

  18. Zhang, J., Yang, H., Long, M., Li, L. & Dean, A. M. Evolution of enzymatic activities of testis-specific short-chain dehydrogenase/reductase in Drosophila. J. Mol. Evol. 71, 241–249 (2010).

    Article  CAS  PubMed  Google Scholar 

  19. Matsuno, M. et al. Evolution of a novel phenolic pathway for pollen development. Science 325, 1688–1692 (2009).

    Article  CAS  PubMed  Google Scholar 

  20. Weng, J. K., Li, Y., Mo, H. P. & Chapple, C. Assembly of an evolutionarily new pathway for α-pyrone biosynthesis in Arabidopsis. Science 337, 960–964 (2012). References 19 and 20 describe the development of a new metabolic pathway as a consequence of new-gene duplication.

    Article  CAS  PubMed  Google Scholar 

  21. Rosso, L. et al. Birth and rapid subcellular adaptation of a hominoid-specific CDC14 protein. PLoS Biol. 6, e140 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Elde, N. C., Morgan, G., Winey, M., Sperling, L. & Turkewitz, A. P. Elucidation of clathrin-mediated endocytosis in tetrahymena reveals an evolutionarily convergent recruitment of dynamin. PLoS Genet. 1, e52 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Elde, N. C., Long, M. & Turkewitz, A. P. A role for convergent evolution in the secretory life of cells. Trends Cell Biol. 17, 157–164 (2007).

    Article  CAS  PubMed  Google Scholar 

  24. Kumarasamy, K. K. et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect. Dis. 10, 597–602 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Emerson, J. J., Cardoso-Moreira, M., Borevitz, J. O. & Long, M. Natural selection shapes genome-wide patterns of copy-number polymorphism in Drosophila melanogaster. Science 320, 1629–1631 (2008).

    Article  CAS  PubMed  Google Scholar 

  26. Daborn, P. J. et al. A single p450 allele associated with insecticide resistance in Drosophila. Science 297, 2253–2256 (2002).

    Article  CAS  PubMed  Google Scholar 

  27. Bergelson, J., Kreitman, M., Stahl, E. A. & Tian, D. C. Evolutionary dynamics of plant R-genes. Science 292, 2281–2285 (2001).

    Article  CAS  PubMed  Google Scholar 

  28. Takken, F. L. & Joosten, M. H. Plant resistance genes: their structure, function and evolution. Eur. J. Plant Pathol. 106, 699–713 (2000).

    Article  CAS  Google Scholar 

  29. Sayah, D. M., Sokolskaja, E., Berthoux, L. & Luban, J. Cyclophilin A retrotransposition into TRIM5 explains owl monkey resistance to HIV-1. Nature 430, 569–573 (2004).

    Article  CAS  PubMed  Google Scholar 

  30. Stremlau, M. et al. The cytoplasmic body component TRIM5α restricts HIV-1 infection in Old World monkeys. Nature 427, 848–853 (2004).

    Article  CAS  PubMed  Google Scholar 

  31. Chen, L., DeVries, A. L. & Cheng, C. H. C. 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 

  32. Chen, L., DeVries, A. L. & Cheng, C. H. Convergent evolution of antifreeze glycoproteins in Antarctic notothenioid fish and Arctic cod. Proc. Natl Acad. Sci. USA 94, 3817–3822 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Cheng, C. H. & Chen, L. Evolution of an antifreeze glycoprotein. Nature 401, 443–444 (1999).

    Article  CAS  PubMed  Google Scholar 

  34. Wolpert, L. et al. Principles of Development 2nd edn (Oxford Univ. Press, 2002).

    Google Scholar 

  35. King, M. & Wilson, A. Evolution at two levels in humans and chimpanzees. Science 188, 107–116 (1975).

    Article  CAS  PubMed  Google Scholar 

  36. Guss, K. A., Nelson, C. E., Hudson, A., Kraus, M. E. & Carroll, S. B. Control of a genetic regulatory network by a selector gene. Science 292, 1164–1167 (2001).

    Article  CAS  PubMed  Google Scholar 

  37. Carroll, S. B. Evolution at two levels: on genes and form. PLoS Biol 3, e245 (2005).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. King, N. et al. The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans. Nature 451, 783–788 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Srivastava, M. et al. The Amphimedon queenslandica genome and the evolution of animal complexity. Nature 466, 720–726 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Sulston, J. E. & Horvitz, H. R. Post-embryonic cell lineages of the nematode, Caenorhabditis elegans. Dev. Biol. 56, 110–156 (1977).

    Article  CAS  PubMed  Google Scholar 

  41. Stauber, M., Jackle, H. & Schmidt-Ott, U. The anterior determinant bicoid of Drosophila is a derived Hox class 3 gene. Proc. Natl Acad. Sci. USA 96, 3786–3789 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Stauber, M., Taubert, H. & Schmidt-Ott, U. Function of bicoid and hunchback homologs in the basal cyclorrhaphan fly Megaselia (Phoridae). Proc. Natl Acad. Sci. USA 97, 10844–10849 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Lemke, S. et al. Maternal activation of gap genes in the hover fly Episyrphus. Development 137, 1709–1719 (2010).

    Article  CAS  PubMed  Google Scholar 

  44. Heinen, T. J. A. J., Staubach, F., Haming, D. & Tautz, D. Emergence of a new gene from an intergenic region. Curr. Biol. 19, 1527–1531 (2009). This reports the remarkable phenotypic effects of a non-coding RNA gene that recently appeared in the house mouse and its close relatives and that, if knocked out, leads to reduced sperm motility and reduced testis weight.

    Article  CAS  PubMed  Google Scholar 

  45. Joppich, C., Scholz, S., Korge, G. & Schwendemann, A. Umbrea, a chromo shadow domain protein in Drosophila melanogaster heterochromatin, interacts with Hip, HP1 and HOAP. Chromosome Res. 17, 19–36 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Chen, S., Zhang, Y. E. & Long, M. New genes in Drosophila quickly become essential. Science 330, 1682–1685 (2010). This article describes a large-scale experiment that investigates the phenotypic effects of 195 new genes in D. melanogaster using RNAi-mediated knockdown, revealing that a high proportion of these recently evolved genes have evolved essential developmental functions.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Saleem, S. et al. Drosophila melanogaster p24 trafficking proteins have vital roles in development and reproduction. Mech. Dev. 129, 177–191 (2012).

    Article  CAS  PubMed  Google Scholar 

  48. Miklos, G. L. & Rubin, G. M. The role of the genome project in determining gene function: insights from model organisms. Cell 86, 521–529 (1996).

    Article  CAS  PubMed  Google Scholar 

  49. Perrimon, N., Lanjuin, A., Arnold, C. & Noll, E. Zygotic lethal mutations with maternal effect phenotypes in Drosophila melanogaster. II. Loci on the second and third chromosomes identified by P-element-induced mutations. Genetics 144, 1681–1692 (1996).

    PubMed  PubMed Central  CAS  Google Scholar 

  50. Dowell, R. D. et al. Genotype to phenotype: a complex problem. Science 328, 469 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Mummery-Widmer, J. L. et al. Genome-wide analysis of Notch signalling in Drosophila by transgenic RNAi. Nature 458, 987–992 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Schnorrer, F. et al. Systematic genetic analysis of muscle morphogenesis and function in Drosophila. Nature 464, 287–291 (2010).

    Article  CAS  PubMed  Google Scholar 

  53. Makino, T., Hokamp, K. & McLysaght, A. The complex relationship of gene duplication and essentiality. Trends Genet. 25, 152–155 (2009).

    Article  CAS  PubMed  Google Scholar 

  54. Lott, S. E., Kreitman, M., Palsson, A., Alekseeva, E. & Ludwig, M. Z. Canalization of segmentation and its evolution in Drosophila. Proc. Natl Acad. Sci. USA 104, 10926–10931 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Coyne, J. A. & Orr, H. A. Speciation (Sinauer Associates Sunderland, 2004).

    Google Scholar 

  56. Gould, S. J. Ontogeny and Phylogeny (Belknap, 1977).

    Google Scholar 

  57. Domazet-Lošo, T. & Tautz, D. A phylogenetically based transcriptome age index mirrors ontogenetic divergence patterns. Nature 468, 815–818 (2010).

    Article  CAS  PubMed  Google Scholar 

  58. Kalinka, A. T. et al. Gene expression divergence recapitulates the developmental hourglass model. Nature 468, 811–814 (2010).

    Article  CAS  PubMed  Google Scholar 

  59. Lemke, S. et al. bicoid occurrence and Bicoid-dependent hunchback regulation in lower cyclorrhaphan flies. Evol. Dev. 10, 413–420 (2008).

    Article  CAS  PubMed  Google Scholar 

  60. Park, J.-I. et al. Origin of INSL3-mediated testicular descent in therian mammals. Genome Res. 18, 974–985 (2008). This evolutionary analysis reveals that an important physiological phenotype in therian mammals — the testicular descent — was derived with a new gene duplicate, INSL3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. McGowan, B. M. et al. Relaxin-3 stimulates the hypothalamic-pituitary-gonadal axis. Am. J. Physiol. Endocrinol. Metab. 295, 278–286 (2008).

    Article  CAS  Google Scholar 

  62. Arroyo, J. I., Hoffmann, F. G., Good, S. & Opazo, J. C. INSL4 pseudogenes help define the relaxin family repertoire in the common ancestor of placental mammals. J. Mol. Evol. 75, 73–78 (2012).

    Article  CAS  PubMed  Google Scholar 

  63. Johnson, R. M. et al. Phylogenetic comparisons suggest that distance from the locus control region guides developmental expression of primate β-type globin genes. Proc. Natl Acad. Sci. USA 103, 3186–3191 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Kawasaki, K., Lafont, A.-G. & Sire, J.-Y. The evolution of milk casein genes from tooth genes before the origin of mammals. Mol. Biol. Evol. 28, 2053–2061 (2011).

    Article  CAS  PubMed  Google Scholar 

  65. Meslin, C. et al. The evolutionary history of the SAL1 gene family in eutherian mammals. BMC Evol. Biol. 11, 148 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Parker, H. G. et al. An expressed fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs. Science 325, 995–998 (2009). This paper describes a young phenotype in dogs that is derived from a newly retrotransposed gene.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  67. Zhang, Y. E., Vibranovski, M. D., Landback, P., Marais, G. A. B. & Long, M. Chromosomal redistribution of male-biased genes in mammalian evolution with two bursts of gene gain on the X chromosome. PLoS Biol. 8, e1000494 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Church, D. M. et al. Lineage-specific biology revealed by a finished genome assembly of the mouse. PLoS Biol. 7, e1000112 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Nurminsky, D. I., Nurminskaya, M. V., De Aguiar, D. & Hartl, D. L. Selective sweep of a newly evolved sperm-specific gene in Drosophila. Nature 396, 572–575 (1998).

    Article  CAS  PubMed  Google Scholar 

  70. Yeh, S.-D., Do, T., Abbassi, M. & Ranz, J. M. Functional relevance of the newly evolved sperm dynein intermediate chain multigene family in Drosophila melanogaster males. Commun. Integr. Biol. 5, 462–465 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  71. Yeh, S.-D. et al. Functional evidence that a recently evolved Drosophila sperm-specific gene boosts sperm competition. Proc. Natl Acad. Sci. USA 109, 2043–2048 (2012). This reports an elegant experiment that detects an interesting phenotypic effect of a species-specific locus on sperm competition in D. melanogaster.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Yasuda, G. K., Schubiger, G. & Wakimoto, B. T. Genetic characterization of ms(3)K81, a paternal effect gene of Drosophila melanogaster. Genetics 140, 219–229 (1995).

    PubMed  PubMed Central  CAS  Google Scholar 

  73. Loppin, B., Lepetit, D., Dorus, S., Couble, P. & Karr, T. L. Origin and neofunctionalization of a Drosophila paternal effect gene essential for zygote viability. Curr. Biol. 15, 87–93 (2005). This article describes the first-known essential paternal new gene that originated in the ancestor of the species in the D. melanogaster subgroup.

    Article  CAS  PubMed  Google Scholar 

  74. Bai, Y., Casola, C., Feschotte, C. & Betran, E. Comparative genomics reveals a constant rate of origination and convergent acquisition of functional retrogenes in Drosophila. Genome Biol. 8, R11 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Quezada-Diaz, J. E., Muliyil, T., Rio, J. & Betran, E. Drcd-1 related: a positively selected spermatogenesis retrogene in Drosophila. Genetica 138, 925–937 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  76. Chen, S. D. et al. Frequent recent origination of brain genes shaped the evolution of foraging behavior in Drosophila. Cell Rep. 1, 118–132 (2012). This experimental analysis of a large number of new genes that are expressed in the D. melanogaster brain reveals the significant impact on the evolution of new brain structure and the explicit roles of these genes in shaping foraging behaviours through expression in neurons.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. Chen, Y., Dai, H. Z., Chen, S. D., Zhang, L. Y. & Long, M. Y. Highly tissue specific expression of Sphinx supports its male courtship related role in Drosophila melanogaster. PLoS ONE 6, e18853 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Long, M., Vibranovski, M. D. & Zhang, Y. in Rapidly Evolving Genes and Genetic Systems (eds Singh, R., Xu, J. & Kulanthinal, R.) 101–114 (Oxford Univ. Press, 2012).

    Book  Google Scholar 

  79. Betran, E. Retroposed new genes out of the X in Drosophila. Genome Res. 12, 1854–1859 (2002).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  80. Emerson, J., Kaessmann, H., Betrán, E. & Long, M. Extensive gene traffic on the mammalian X chromosome. Science 303, 537–540 (2004).

    Article  CAS  PubMed  Google Scholar 

  81. Zhang, Y. E., Vibranovski, M. D., Krinsky, B. H. & Long, M. Age-dependent chromosomal distribution of male-biased genes in Drosophila. Genome Res. 20, 1526–1533 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Dai, H., Yoshimatsu, T. & Long, M. Retrogene movement within- and between-chromosomes in the evolution of Drosophila genomes. Gene 385, 96–102 (2006).

    Article  CAS  PubMed  Google Scholar 

  83. Vibranovski, M. D., Zhang, Y. & Long, M. General gene movement off the X chromosome in the Drosophila genus. Genome Res. 19, 897–903 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. Meisel, R. P., Han, M. V. & Hahn, M. W. A complex suite of forces drives gene traffic from Drosophila X chromosomes. Genome Biol. Evol. 1, 176–188 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Schrider, D. R. et al. Gene copy-number polymorphism caused by retrotransposition in humans. PLoS Genet. 9, e1003242 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Schrider, D. R., Stevens, K., Cardeno, C. M., Langley, C. H. & Hahn, M. W. Genome-wide analysis of retrogene polymorphisms in Drosophila melanogaster. Genome Res. 21, 2087–2095 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Baker, R. H. & Wilkinson, G. S. Comparative genomic hybridization (CGH) reveals a neo-X chromosome and biased gene movement in stalk-eyed flies (genus Teleopsis). PLoS Genet. 6, e1001121 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Wang, J., Long, M. & Vibranovski, M. D. Retrogenes moved out of the Z chromosome in the silkworm. J. Mol. Evol. 74, 1–14 (2012).

    Article  CAS  Google Scholar 

  89. Ranz, J. M., Castillo-Davis, C. I., Meiklejohn, C. D. & Hartl, D. L. Sex-dependent gene expression and evolution of the Drosophila transcriptome. Science 300, 1742–1745 (2003).

    Article  CAS  PubMed  Google Scholar 

  90. Parisi, M. et al. Paucity of genes on the Drosophila X chromosome showing male-biased expression. Science 299, 697–700 (2003).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Baker, D. A. & Russell, S. Role of testis-specific gene expression in sex-chromosome evolution of Anopheles gambiae. Genetics 189, 1117–1120 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Magnusson, K. et al. Demasculinization of the Anopheles gambiae X chromosome. BMC Evol. Biol. 12, 69–69 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  93. Toups, M. A. & Hahn, M. W. Retrogenes reveal the direction of sex-chromosome evolution in mosquitoes. Genetics 186, 763–766 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Khil, P. P., Smirnova, N. A., Romanienko, P. J. & Camerini-Otero, R. D. The mouse X chromosome is enriched for sex-biased genes not subject to selection by meiotic sex chromosome inactivation. Nature Genet. 36, 642–646 (2004).

    Article  CAS  PubMed  Google Scholar 

  95. Vibranovski, M. D., Lopes, H. F., Karr, T. L. & Long, M. Stage-specific expression profiling of Drosophila spermatogenesis suggests that meiotic sex chromosome inactivation drives genomic relocation of testis-expressed genes. PLoS Genet. 5, e1000731 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Vibranovski, M. D., Chalopin, D. S., Lopes, H. F., Long, M. & Karr, T. L. Direct evidence for postmeiotic transcription during Drosophila melanogaster spermatogenesis. Genetics 186, 431–433 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Vibranovski, M. D. et al. Re-analysis of the larval testis data on meiotic sex chromosome inactivation revealed evidence for tissue-specific gene expression related to the Drosophila X chromosome. BMC Biol. 10, 49 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Hense, W., Baines, J. F. & Parsch, J. X chromosome inactivation during Drosophila spermatogenesis. Plos Biol. 5, e273 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Sturgill, D., Zhang, Y., Parisi, M. & Oliver, B. Demasculinization of X chromosomes in the Drosophila genus. Nature 450, 238–241 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  100. Wu, C. I. & Xu, E. Y. Sexual antagonism and X inactivation--the SAXI hypothesis. Trends Genet. 19, 243–247 (2003).

    Article  CAS  PubMed  Google Scholar 

  101. Vicoso, B. & Charlesworth, B. The deficit of male-biased genes on the D. melanogaster X chromosome is expression-dependent: a consequence of dosage compensation? J. Mol. Evol. 68, 576–583 (2009).

    Article  CAS  PubMed  Google Scholar 

  102. Bachtrog, D., Toda, N. R. T. & Lockton, S. Dosage compensation and demasculinization of X chromosomes in Drosophila. Curr. Biol. 20, 1476–1481 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Diaz-Castillo, C. & Ranz, J. M. Nuclear chromosome dynamics in the Drosophila male germ line contribute to the nonrandom genomic distribution of retrogenes. Mol. Biol. Evol. 29, 2105–2108 (2012).

    Article  CAS  PubMed  Google Scholar 

  104. Brand, A. H. & Perrimon, N. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118, 401–415 (1993).

    CAS  PubMed  Google Scholar 

  105. Strausfeld, N. J. & Li, Y. Organization of olfactory and multimodal afferent neurons supplying the calyx and pedunculus of the cockroach mushroom bodies. J. Comp. Neurol. 409, 603–625 (1999).

    Article  CAS  PubMed  Google Scholar 

  106. Strausfeld, N. J. & Li, Y. Representation of the calyces in the medial and vertical lobes of cockroach mushroom bodies. J. Comp. Neurol. 409, 626–646 (1999).

    Article  CAS  PubMed  Google Scholar 

  107. Fortna, A. et al. Lineage-specific gene duplication and loss in human and great ape evolution. PLoS Biol. 2, e207 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  108. Sudmant, P. H. et al. Diversity of human copy number variation and multicopy genes. Science 330, 641–646 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Dennis, M. Y. et al. Evolution of human-specific neural SRGAP2 genes by incomplete segmental duplication. Cell 149, 912–922 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Charrier, C. et al. Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation. Cell 149, 923–935 (2012). This article details the remarkable neuronal effects of human-specific SRGAP2 duplicates on the mouse brain, implicating a possible function in the human brain.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  111. Wang, W. et al. Origin of sphinx, a young chimeric RNA gene in Drosophila melanogaster. Proc. Natl Acad. Sci. USA 99, 4448–4453 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Dai, H. et al. The evolution of courtship behaviors through the origination of a new gene in Drosophila. Proc. Natl Acad. Sci. USA 105, 7478–7483 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Benton, R., Vannice, K. S., Gomez-Diaz, C. & Vosshall, L. B. Variant ionotropic glutamate receptors as chemosensory receptors in Drosophila. Cell 136, 149–162 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  114. Hallem, E. A. & Carlson, J. R. Coding of odors by a receptor repertoire. Cell 125, 143–160 (2006).

    Article  CAS  PubMed  Google Scholar 

  115. Kitamoto, T. Conditional modification of behavior in Drosophila by targeted expression of a temperature-sensitive shibire allele in defined neurons. J. Neurobiol. 47, 81–92 (2001).

    Article  CAS  PubMed  Google Scholar 

  116. Kim, J., Kim, I., Han, S. K., Bowie, J. U. & Kim, S. Network rewiring is an important mechanism of gene essentiality change. Sci. Rep. 2, 900 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  117. Jeong, H., Mason, S. P., Barabasi, A. L. & Oltvai, Z. N. Lethality and centrality in protein networks. Nature 411, 41–42 (2001).

    Article  CAS  PubMed  Google Scholar 

  118. Ross, B. D. et al. Stepwise evolution of essential centromere function in a Drosophila neogene. Science 340, 1211–1214 (2013). This reports a clear neofunctionalization process in which a species-specific centromere-targeting gene in D. melanogaster, Umbrea , was generated by a domain-deleted duplicate and a rewiring process under natural selection.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  119. Konikoff, C. E., Wisotzkey, R. G., Stinchfield, M. J. & Newfeld, S. J. Distinct molecular evolutionary mechanisms underlie the functional diversification of the Wnt and TGFβ signaling pathways. J. Mol. Evol. 70, 303–312 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  120. Li, D. et al. A de novo originated gene depresses budding yeast mating pathway and is repressed by the protein encoded by its antisense strand. Cell Res. 20, 408–420 (2010).

    Article  CAS  PubMed  Google Scholar 

  121. Capra, J., Pollard, K. S. & Singh, M. Novel genes exhibit distinct patterns of function acquisition and network integration. Genome Biol. 11, R127 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  122. Chen, S. D. et al. Reshaping of global gene expression networks and sex-biased gene expression by integration of a young gene. EMBO J. 31, 2798–2809 (2012). This article provides strong experimental evidence that new genes can reshape gene expression networks in short evolutionary time under positive selection.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Lu, J. et al. The birth and death of microRNA genes in Drosophila. Nature Genet. 40, 351–355 (2008).

    Article  CAS  PubMed  Google Scholar 

  124. Betran, E. & Long, M. Dntf-2r, a young Drosophila retroposed gene with specific male expression under positive Darwinian selection. Genetics 164, 977–988 (2003).

    PubMed  PubMed Central  CAS  Google Scholar 

  125. Ni, X. et al. Adaptive evolution and the birth of CTCF binding sites in the Drosophila genome. PLoS Biol. 10, e1001420 (2012). This is the first genome-wide experiment to reveal rapid evolution of a regulatory mechanism of insulation with new genes in Drosophila spp.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  126. Almada, A. E., Wu, X., Kriz, A. J., Burge, C. B. & Sharp, P. A. Promoter directionality is controlled by U1 snRNP and polyadenylation signals. Nature 499, 360–363 (2013). This is the first report of a significant linear correlation between the age of genes and two critical signals to define transcription units, U1 small nuclear ribonucleoprotein recognition sites and polyadenylation sites (PAS) in vertebrates. Directional gain of the U1 sites and loss of PAS sites revealed how a new gene acquires its U1–PAS axis for a productive transcription under natural selection.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. Chen, S., Yang, H., Krinsky, B. H., Zhang, A. & Long, M. Roles of young serine-endopeptidase genes in survival and reproduction revealed rapid evolution of phenotypic effects at adult stages. Fly 5, 345–351 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  128. Wainszelbaum, M. J. et al. TBC1D3, a hominoid-specific gene, delays IRS-1 degradation and promotes insulin signaling by modulating p70 S6 kinase activity. PLoS ONE 7, e31225 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  129. Nowick, K., Hamilton, A. T., Zhang, H., Stubbs, L. Rapid sequence and expression divergence suggest selection for novel function in primate-specific KRAB-ZNF genes. Mol. Biol. Evol. 27, 2606–2617 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  130. Duret, L. et al. The Xist RNA gene evolved in eutherians by pseudogenization of a protein-coding gene. Science 312, 1653–1655 (2006).

    Article  CAS  PubMed  Google Scholar 

  131. Mi, S. et al. Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature 403, 785–789 (2000).

    Article  CAS  PubMed  Google Scholar 

  132. Surridge, A. K., Osorio, D. & Mondy, N. I. Evolution and selection of trichromatic vision in primates. Trends Ecol. Evol. 18, 198–205 (2003).

    Article  Google Scholar 

  133. Niimura, Y. & Nei, M. Extensive gains and losses of olfactory receptor genes in mammalian evolution. PLoS ONE 2, e708 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  134. Rollmann, S.M. et al. Odorant receptor polymorphisms and natural variation behavior in Drosophila melanogaster. Genetics 186: 687–697 (2010)

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgements

The authors are indebted to their collaborators, A. Dean, K. White, T. Karr, L. Luo and L. Li, for their intellectual and technical support. The authors thank X. Ni, Y. Zhang, M. Vibranovski, M. Spletter and P. Landback for their efforts and contributions to the understanding of new genes and their role in phenotypic evolution. The authors also thank C. Kemkemer, N. VanKuren, S. Newfeld and A. Turkewitz for their discussions. M.L. was supported by the US National Institutes of Health (NIH) and the US National Science Foundation (NSF) grants (1R01100768-01A1, MCB1051826, MCB1026200); S.C. was supported by the NSF dissertation improvement grant (DEB-1110607), and B.H.K. by the NIH Genetics Training grant (T32 GM007197) and a US Department of Education GAANN Fellowship.

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Authors and Affiliations

  1. Department of Ecology and Evolution, The University of Chicago, 1101 East 57th Street, Chicago, 60637, Illinois, USA

    Sidi Chen & Manyuan Long

  2. Department of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, 02139, Massachusetts, USA

    Sidi Chen

  3. Committee on Evolutionary Biology, The University of Chicago, 1101 East 57th Street, Chicago, 60637, Illinois, USA

    Benjamin H. Krinsky & Manyuan Long

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  1. Sidi Chen
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Glossary

Retrotransposition

An RNA-based duplication mechanism that involves the transcription and processing of a gene into an mRNA that is then reverse transcribed and integrated into a new DNA locus in a genome.

Mutation selection

An evolutionary process in which selection acts on a mutation to determine its eventual fate.

Hominoid

A kind of primate species including the great hominoids (humans, chimpanzees, gorillas and orang-utans) and lesser hominoids (gibbons and siamangs).

Convergent evolution

The evolution of two unrelated lineages such that they share a similar phenotype.

Maternal-effect morphogen

A gene product from a maternal-effect gene; for example, Bicoid in Drosophila spp. is a developmental signal for which the concentration has an impact on embryonic growth.

Clade

A group of closely related species in an evolutionary tree.

Outgroup

A group of reference organisms outside of a group of organisms that are being analysed for their evolutionary relationship.

Ontogeny

The development of an organism.

Phylogeny

A tree of life that records the evolutionary history of a group of species.

Phylotypic stage

A developmental stage in which the embryos of different species resemble each other in morphology.

Phylostratigraphy

A statistical method that traces genes back to their most ancient ancestors to study macroevolutionary patterns.

Hourglass model

A developmental model that uses analogy to the hourglass to describe the interspecies divergence of phenotypes during the entire developmental process. In this model, the initial and final stages are divergent between species, whereas the intermediate phylotypic stage is the most evolutionarily conserved.

Gene traffic

A directional gene duplication process between the sex chromosomes and autosomes. It often confers sex-biased expression on the genes.

Therian mammals

A group of mammalian species consisting of marsupial and placental animals.

Catarrhine primates

A group of primate species that comprises the Old World monkeys, higher apes and hominoids.

Chondrodysplasia

A hereditary skeletal disorder that results in limited development and a deformity in morphology.

Selective sweep

A strong directional selection that happened recently and rapidly elevated the frequencies of advantageous alleles in a population.

Paternal-effect gene

A paternal gene that affects the phenotype of the offspring, irrespective of the offspring genotype.

Pleiotropic

Pertaining to a gene or mutation having multiple phenotypic effects.

Sexual antagonism

The phenomenon whereby a mutation has opposite phenotypic effects on males and females.

Dosage compensation

A process that equalizes the expression levels of the genes on the sex chromosomes, either between males and females or between the sex chromosomes and autosomes.

Enhancer trap

A transgenic construct used to identify enhancer elements for a gene that is expressed in specific tissues. Insertion of the construct near a tissue-specific enhancer results in the tissue-specific expression of the reporter gene.

Hubs

The nodes with many interactions in gene networks.

The centrality–lethality rule

The proposal put forward by Jeong, Mason, Barabasi and Otavi that the genes in the hub positions in gene networks are associated with lethal phenotypes when silenced, suggesting that those genes have essential functions.

Ka/Ks ratio

The ratio of the number of substitutions at non-synonymous sites to the number of substitutions at synonymous sites.

McDonald–Kreitman test

A molecular population genetics test to detect positive selection using a statistical test of the null hypothesis of neutrality.

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Chen, S., Krinsky, B. & Long, M. New genes as drivers of phenotypic evolution. Nat Rev Genet 14, 645–660 (2013). https://doi.org/10.1038/nrg3521

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