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Open questions in the study of de novo genes: what, how and why - Nature Reviews Genetics

  • ️Hurst, Laurence D.
  • ️Mon Jul 25 2016
  • Levine, M. T., Jones, C. D., Kern, A. D., Lindfors, H. A. & Begun, D. J. Novel genes derived from noncoding DNA in Drosophila melanogaster are frequently X-linked and exhibit testis-biased expression. Proc. Natl Acad. Sci. USA 103, 9935–9939 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Begun, D. J., Lindfors, H. A., Thompson, M. E. & Holloway, A. K. Recently evolved genes identified from Drosophila yakuba and D. erecta accessory gland expressed sequence tags. Genetics 172, 1675–1681 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xiao, W. et al. A rice gene of de novo origin negatively regulates pathogen-induced defense response. PLoS ONE 4, e4603 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Knowles, D. G. & McLysaght, A. Recent de novo origin of human protein-coding genes. Genome Res. 19, 1752–1759 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li, L. et al. Identification of the novel protein QQS as a component of the starch metabolic network in Arabidopsis leaves. Plant J. 58, 485–498 (2009).

    Article  CAS  PubMed  Google Scholar 

  • Cai, J., Zhao, R., Jiang, H. & Wang, W. De novo origination of a new protein-coding gene in Saccharomyces cerevisiae. Genetics 179, 487–496 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou, Q. & Wang, W. On the origin and evolution of new genes — a genomic and experimental perspective. J. Genet. Genom. 35, 639–648 (2008).

    Article  CAS  Google Scholar 

  • Toll-Riera, M. et al. Origin of primate orphan genes: a comparative genomics approach. Mol. Biol. Evol. 26, 603–612 (2009).

    Article  CAS  PubMed  Google Scholar 

  • Wu, D.-D., Irwin, D. M. & Zhang, Y.-P. De novo origin of human protein-coding genes. PLoS Genet. 7, e1002379 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tautz, D. & Domazet-Loso, T. The evolutionary origin of orphan genes. Nat. Rev. Genet. 12, 692–702 (2011).

    Article  CAS  PubMed  Google Scholar 

  • McLysaght, A. & Guerzoni, D. New genes from non-coding sequence: the role of de novo protein-coding genes in eukaryotic evolutionary innovation. Phil. Trans. R. Soc. B 370, 20140332 (2015).

    Article  CAS  PubMed  Google Scholar 

  • Schlötterer, C. Genes from scratch — the evolutionary fate of de novo genes. Trends Genet. 31, 215–219 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guerzoni, D. & McLysaght, A. De novo genes arise at a slow but steady rate along the primate lineage and have been subject to incomplete lineage sorting. Genome Biol. Evol. 8, 1222–1232 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Domazet-Loso, T., Brajkovic´, J. & Tautz, D. A phylostratigraphy approach to uncover the genomic history of major adaptations in metazoan lineages. Trends Genet. 23, 533–539 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Wolfe, K. Evolutionary genomics: yeasts accelerate beyond BLAST. Curr. Biol. 14, R392–R394 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Elhaik, E., Sabath, N. & Graur, D. The “inverse relationship between evolutionary rate and age of mammalian genes” is an artifact of increased genetic distance with rate of evolution and time of divergence. Mol. Biol. Evol. 23, 1–3 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Moyers, B. A. & Zhang, J. Phylostratigraphic bias creates spurious patterns of genome evolution. Mol. Biol. Evol. 32, 258–267 (2015).

    Article  PubMed  Google Scholar 

  • Moyers, B. A. & Zhang, J. Evaluating phylostratigraphic evidence for widespread de novo gene birth in genome evolution. Mol. Biol. Evol. 33, 1245–1256 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carvunis, A.-R. et al. Proto-genes and de novo gene birth. Nature 487, 370–374 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neme, R. & Tautz, D. Phylogenetic patterns of emergence of new genes support a model of frequent de novo evolution. BMC Genomics 14, 117 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alba, M. M. & Castresana, J. On homology searches by protein Blast and the characterization of the age of genes. BMC Evol. Biol. 7, 53 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Alba, M. M. & Castresana, J. Inverse relationship between evolutionary rate and age of mammalian genes. Mol. Biol. Evol. 22, 598–606 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Domazet-Loso, T. & Tautz, D. An ancient evolutionary origin of genes associated with human genetic diseases. Mol. Biol. Evol. 25, 2699–2707 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Smith, N. G. C. & Eyre-Walker, A. Human disease genes: patterns and predictions. Gene 318, 169–175 (2003).

    Article  CAS  PubMed  Google Scholar 

  • ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57–74 (2012).

  • Hurst, L. D. Open questions: a logic (or lack thereof) of genome organization. BMC Biol. 11, 58 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  • Graur, D. et al. On the immortality of television sets: 'function' in the human genome according to the evolution-free gospel of ENCODE. Genome Biol. Evol. 5, 578–590 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Doolittle, W. F. Is junk DNA bunk? A critique of ENCODE. Proc. Natl Acad. Sci. USA 110, 5294–5300 (2013).

    Article  CAS  PubMed  Google Scholar 

  • Jaillon, O. et al. Translational control of intron splicing in eukaryotes. Nature 451, 359–362 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Cusack, B. P., Arndt, P. F., Duret, L. & Roest Crollius, H. Preventing dangerous nonsense: selection for robustness to transcriptional error in human genes. PLoS Genet. 7, e1002276 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dewey, C. N., Rogozin, I. B. & Koonin, E. V. Compensatory relationship between splice sites and exonic splicing signals depending on the length of vertebrate introns. BMC Genomics 7, 311 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schüler, A., Ghanbarian, A. T. & Hurst, L. D. Purifying selection on splice-related motifs, not expression level nor RNA folding, explains nearly all constraint on human lincRNAs. Mol. Biol. Evol. 31, 3164–3183 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ruiz-Orera, J., Messeguer, X., Subirana, J. A. & Alba, M. M. Long non-coding RNAs as a source of new peptides. eLife 3, e03523 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, J.-Y. et al. Emergence, retention and selection: a trilogy of origination for functional de novo proteins from ancestral lncRNAs in primates. PLoS Genet. 11, e1005391 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao, L., Saelao, P., Jones, C. D. & Begun, D. J. Origin and spread of de novo genes in Drosophila melanogaster populations. Science 343, 769–772 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Galtier, N., Duret, L., Glémin, S. & Ranwez, V. GC-biased gene conversion promotes the fixation of deleterious amino acid changes in primates. Trends Genet. 25, 1–5 (2009).

    Article  CAS  PubMed  Google Scholar 

  • Blomen, V. A. et al. Gene essentiality and synthetic lethality in haploid human cells. Science 350, 1092–1096 (2015).

    Article  CAS  PubMed  Google Scholar 

  • Wang, T. et al. Identification and characterization of essential genes in the human genome. Science 350, 1096–1101 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, J. et al. Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells. Nature 516, 405–409 (2014).

    Article  CAS  PubMed  Google Scholar 

  • Lavialle, C. et al. Paleovirology of 'syncytins', retroviral env genes exapted for a role in placentation. Phil. Trans. R. Soc. B 368, 20120507 (2013).

    Article  CAS  PubMed  Google Scholar 

  • Li, D., Yan, Z., Lu, L., Jiang, H. & Wang, W. Pleiotropy of the de novo-originated gene MDF1. Sci. Rep. 4, 7280 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 

  • Ghysen, A. Debatable issues. Interview with L Wolpert and A García-Bellido. Int. J. Dev. Biol. 42, 511–518 (1998).

    Google Scholar 

  • Tautz, D. A genetic uncertainty problem. Trends Genet. 16, 475–477 (2000).

    Article  CAS  PubMed  Google Scholar 

  • Chalfin, L. et al. Mapping ecologically relevant social behaviours by gene knockout in wild mice. Nat. Commun. 5, 4569 (2014).

    Article  CAS  PubMed  Google Scholar 

  • Xu, J. & Zhang, J. Are human translated pseudogenes functional? Mol. Biol. Evol. 33, 755–760 (2016).

    Article  CAS  PubMed  Google Scholar 

  • Chen, S., Zhang, Y. E. & Long, M. New genes in Drosophila quickly become essential. Science 330, 1682–1685 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Bird, A. P. Gene number, noise reduction and biological complexity. Trends Genet. 11, 94–100 (1995).

    Article  CAS  PubMed  Google Scholar 

  • Hurst, L. D. Evolutionary genomics and the reach of selection. J. Biol. 8, 12 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prestridge, D. S. & Burks, C. The density of transcriptional elements in promoter and non-promoter sequences. Hum. Mol. Genet. 2, 1449–1453 (1993).

    Article  CAS  PubMed  Google Scholar 

  • Hoekstra, H. E. & Coyne, J. A. The locus of evolution: evo devo and the genetics of adaptation. Evolution 61, 995–1016 (2007).

    Article  PubMed  Google Scholar 

  • Begun, D. J., Lindfors, H. A., Kern, A. D. & Jones, C. D. Evidence for de novo evolution of testis-expressed genes in the Drosophila yakuba/Drosophila erecta clade. Genetics 176, 1131–1137 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ebisuya, M., Yamamoto, T., Nakajima, M. & Nishida, E. Ripples from neighbouring transcription. Nat. Cell Biol. 10, 1106–1113 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Siepel, A. Darwinian alchemy: human genes from noncoding DNA. Genome Res. 19, 1693–1695 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murphy, D. N. & McLysaght, A. De novo origin of protein-coding genes in murine rodents. PLoS ONE 7, e48650 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gotea, V., Petrykowska, H. M. & Elnitski, L. Bidirectional promoters as important drivers for the emergence of species-specific transcripts. PLoS ONE 8, e57323 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu, X. & Sharp, P. A. Divergent transcription: a driving force for new gene origination? Cell 155, 990–996 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Akiva, P. et al. Transcription-mediated gene fusion in the human genome. Genome Res. 16, 30–36 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parra, G. et al. Tandem chimerism as a means to increase protein complexity in the human genome. Genome Res. 16, 37–44 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nacu, S. et al. Deep RNA sequencing analysis of readthrough gene fusions in human prostate adenocarcinoma and reference samples. BMC Med. Genom. 4, 11 (2011).

    Article  CAS  Google Scholar 

  • Ruiz-Orera, J. et al. Origins of de novo genes in human and chimpanzee. PLoS Genet. 11, e1005721 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neme, R. & Tautz, D. Fast turnover of genome transcription across evolutionary time exposes entire non-coding DNA to de novo gene emergence. eLife 5, e09977 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Necsulea, A. & Kaessmann, H. Evolutionary dynamics of coding and non-coding transcriptomes. Nat. Rev. Genet. 15, 734–748 (2014).

    Article  CAS  PubMed  Google Scholar 

  • Warnecke, T., Huang, Y., Przytycka, T. M. & Hurst, L. D. Unique cost dynamics elucidate the role of frameshifting errors in promoting translational robustness. Genome Biol. Evol. 2, 636–645 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lercher, M. J., Urrutia, A. O., Pavlícek, A. & Hurst, L. D. A unification of mosaic structures in the human genome. Hum. Mol. Genet. 12, 2411–2415 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Wang, J. et al. Sequence features and chromatin structure around the genomic regions bound by 119 human transcription factors. Genome Res. 22, 1798–1812 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, T. et al. Species-specific endogenous retroviruses shape the transcriptional network of the human tumor suppressor protein p53. 104, 18613–18618 (2007).

  • Gotea, V. & Makałowski, W. Do transposable elements really contribute to proteomes? Trends Genet. 22, 260–267 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Thornburg, B. G., Gotea, V. & Makałowski, W. Transposable elements as a significant source of transcription regulating signals. Gene 365, 104–110 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Göke, J. et al. Dynamic transcription of distinct classes of endogenous retroviral elements marks specific populations of early human embryonic cells. Cell Stem Cell 16, 135–141 (2015).

    Article  CAS  PubMed  Google Scholar 

  • Denli, A. M. et al. Primate-specific ORF0 contributes to retrotransposon-mediated diversity. Cell 163, 583–593 (2015).

    Article  CAS  PubMed  Google Scholar 

  • Wang, Y. et al. Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. Dev. Cell 25, 69–80 (2013).

    Article  CAS  PubMed  Google Scholar 

  • Galagan, J. E., & Selker, E. U. RIP: the evolutionary cost of genome defense. Trends Genet. 20, 417–413 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Xie, C. et al. Hominoid-specific de novo protein-coding genes originating from long non-coding RNAs. PLoS Genet. 8, e1002942 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Palmieri, N., Kosiol, C. & Schlötterer, C. The life cycle of Drosophila orphan genes. eLife 3, e01311 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Neme, R. & Tautz, D. Evolution: dynamics of de novo gene emergence. Curr. Biol. 24, R238–R240 (2014).

    Article  CAS  PubMed  Google Scholar 

  • Kamijyo, A., Yura, K. & Ogura, A. Distinct evolutionary rate in the eye field transcription factors found by estimation of ancestral protein structure. Gene 555, 73–79 (2015).

    Article  CAS  PubMed  Google Scholar 

  • Vaquerizas, J. M., Kummerfeld, S. K., Teichmann, S. A. & Luscombe, N. M. A census of human transcription factors: function, expression and evolution. Nat. Rev. Genet. 10, 252–263 (2009).

    Article  CAS  PubMed  Google Scholar 

  • Hayashi, Y., Sakata, H., Makino, Y., Urabe, I. & Yomo, T. Can an arbitrary sequence evolve towards acquiring a biological function? J. Mol. Evol. 56, 162–168 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Zhang, W., Landback, P., Gschwend, A. R., Shen, B. & Long, M. New genes drive the evolution of gene interaction networks in the human and mouse genomes. Genome Biol. 16, 202 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lercher, M. J. & Pál, C. Integration of horizontally transferred genes into regulatory interaction networks takes many million years. Mol. Biol. Evol. 25, 559–567 (2008).

    Article  CAS  PubMed  Google Scholar 

  • Batada, N. N., Hurst, L. D. & Tyers, M. Evolutionary and physiological importance of hub proteins. PLoS Comp. Biol. 2, e88 (2006).

    Article  CAS  Google Scholar 

  • Force, A. et al. Preservation of duplicate genes by complementary, degenerative mutations. Genetics 151, 1531–1545 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schoorlemmer, J., Pérez-Palacios, R., Climent, M., Guallar, D. & Muniesa, P. Regulation of mouse retroelement MuERV-L/MERVL expression by REX1 and epigenetic control of stem cell potency. Front. Oncol. 4, 14 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  • Macfarlan, T. S. et al. Embryonic stem cell potency fluctuates with endogenous retrovirus activity. Nature 487, 57–63 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Imakawa, K., Nakagawa, S. & Miyazawa, T. Baton pass hypothesis: successive incorporation of unconserved endogenous retroviral genes for placentation during mammalian evolution. Genes Cells 20, 771–788 (2015).

    Article  CAS  PubMed  Google Scholar 

  • Aakre, C. D. et al. Evolving new protein-protein interaction specificity through promiscuous intermediates. Cell 163, 594–606 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Esnault, C., Cornelis, G., Heidmann, O. & Heidmann, T. Differential evolutionary fate of an ancestral primate endogenous retrovirus envelope gene, the EnvV syncytin, captured for a function in placentation. PLoS Genet. 9, e1003400 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cornelis, G. et al. Retroviral envelope syncytin capture in an ancestrally diverged mammalian clade for placentation in the primitive Afrotherian tenrecs. Proc. Natl Acad. Sci. USA 111, E4332–E4341 (2014).

    Article  CAS  PubMed  Google Scholar 

  • Cornelis, G. et al. Retroviral envelope gene captures and syncytin exaptation for placentation in marsupials. Proc. Natl Acad. Sci. USA 112, E487–E496 (2015).

    Article  CAS  PubMed  Google Scholar 

  • Cornelis, G. et al. Captured retroviral envelope syncytin gene associated with the unique placental structure of higher ruminants. Proc. Natl Acad. Sci. USA 110, E828–E837 (2013).

    Article  PubMed  Google Scholar 

  • Dupressoir, A., Lavialle, C. & Heidmann, T. From ancestral infectious retroviruses to bona fide cellular genes: role of the captured syncytins in placentation. Placenta 33, 663–671 (2012).

    Article  CAS  PubMed  Google Scholar 

  • Emera, D. et al. Convergent evolution of endometrial prolactin expression in primates, mice, and elephants through the independent recruitment of transposable elements. Mol. Biol. Evol. 29, 239–247 (2012).

    Article  CAS  PubMed  Google Scholar 

  • Maston, G. A. & Ruvolo, M. Chorionic gonadotropin has a recent origin within primates and an evolutionary history of selection. Mol. Biol. Evol. 19, 320–335 (2002).

    Article  CAS  PubMed  Google Scholar 

  • Ross, B. D. et al. Stepwise evolution of essential centromere function in a Drosophila neogene. Science 340, 1211–1214 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Elliot, M. G. & Crespi, B. J. Phylogenetic evidence for early hemochorial placentation in eutheria. Placenta 30, 949–967 (2009).

    Article  CAS  PubMed  Google Scholar 

  • Elliot, M. G. & Crespi, B. J. Genetic recapitulation of human pre-eclampsia risk during convergent evolution of reduced placental invasiveness in eutherian mammals. Phil. Trans. R. Soc. B 370, 20140069 (2015).

    Article  PubMed  Google Scholar 

  • Izsvák, Z., Wang, J., Singh, M., Mager, D. L. & Hurst, L. D. Pluripotency and the endogenous retrovirus HERVH: conflict or serendipity? Bioessays 38, 109–117 (2016).

    Article  PubMed  Google Scholar 

  • Landmann, F., Orsi, G. A., Loppin, B. & Sullivan, W. Wolbachia-mediated cytoplasmic incompatibility is associated with impaired histone deposition in the male pronucleus. PLoS Pathog. 5, e1000343 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fine, P. E. On the dynamics of symbiote-dependent cytoplasmic incompatibility in culicine mosquitoes. J. Invertebr. Pathol. 31, 10–18 (1978).

    Article  CAS  PubMed  Google Scholar 

  • Merrill, C., Bayraktaroglu, L., Kusano, A. & Ganetzky, B. Truncated RanGAP encoded by the Segregation Distorter locus of Drosophila. Science 283, 1742–1745 (1999).

    Article  CAS  PubMed  Google Scholar 

  • Gerdes, K. et al. The hok killer gene family in gram-negative bacteria. New Biol. 2, 946–956 (1990).

    CAS  PubMed  Google Scholar 

  • Hurst, L. D. scat+ is a selfish gene analogous to Medea of Tribolium castaneum. Cell 75, 407–408 (1993).

    Article  CAS  PubMed  Google Scholar 

  • Marshall, J. M. The toxin and antidote puzzle: new ways to control insect pest populations through manipulating inheritance. Bioeng. Bugs 2, 235–240 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen, C.-H. et al. A synthetic maternal-effect selfish genetic element drives population replacement in Drosophila. Science 316, 597–600 (2007).

    Article  CAS  PubMed  Google Scholar 

  • Phadnis, N. & Orr, H. A. A single gene causes both male sterility and segregation distortion in Drosophila hybrids. Science 323, 376–379 (2009).

    Article  CAS  PubMed  Google Scholar 

  • Hurst, L. D. & Pomiankowski, A. Causes of sex ratio bias may account for unisexual sterility in hybrids: a new explanation of Haldane's rule and related phenomena. Genetics 128, 841–858 (1991).

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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 

  • Kosiol, C. et al. Patterns of positive selection in six mammalian genomes. PLoS Genet. 4, e1000144 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goriely, A. et al. Gain-of-function amino acid substitutions drive positive selection of FGFR2 mutations in human spermatogonia. Proc. Natl Acad. Sci. USA 102, 6051–6056 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Suenaga, Y. et al. NCYM, a cis-antisense gene of MYCN, encodes a de novo evolved protein that inhibits GSK3β resulting in the stabilization of MYCN in human neuroblastomas. PLoS Genet. 10, e1003996 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Samusik, N., Krukovskaya, L., Meln, I., Shilov, E. & Kozlov, A. P. PBOV1 is a human de novo gene with tumor-specific expression that is associated with a positive clinical outcome of cancer. PLoS ONE 8, e56162 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zendman, A. J. W., Ruiter, D. J. & Van Muijen, G. N. P. Cancer/testis-associated genes: identification, expression profile, and putative function. J. Cell. Physiol. 194, 272–288 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Simpson, A. J. G., Caballero, O. L., Jungbluth, A., Chen, Y.-T. & Old, L. J. Cancer/testis antigens, gametogenesis and cancer. Nat. Rev. Cancer 5, 615–625 (2005).

    Article  CAS  PubMed  Google Scholar 

  • Hofmann, O. et al. Genome-wide analysis of cancer/testis gene expression. 105, 20422–20427 (2008).

  • Kohn, D. B., Sadelain, M. & Glorioso, J. C. Occurrence of leukaemia following gene therapy of X-linked SCID. Nat. Rev. Cancer 3, 477–488 (2003).

    Article  CAS  PubMed  Google Scholar 

  • Bornberg-Bauer, E. & Alba, M. M. Dynamics and adaptive benefits of modular protein evolution. Curr. Opin. Struct. Biol. 23, 459–466 (2013).

    Article  CAS  PubMed  Google Scholar 

  • Heinen, T. J. A. J., Staubach, F., Häming, D. & Tautz, D. Emergence of a new gene from an intergenic region. Curr. Biol. 19, 1527–1531 (2009).

    Article  CAS  PubMed  Google Scholar 

  • Broustas, C. G. et al. BRCC2, a novel BH3-like domain-containing protein, induces apoptosis in a caspase-dependent manner. J. Biol. Chem. 279, 26780–26788 (2004).

    Article  CAS  PubMed  Google Scholar 

  • Broustas, C. G. et al. The proapoptotic molecule BLID interacts with Bcl-XL and its downregulation in breast cancer correlates with poor disease-free and overall survival. Clin. Cancer Res. 16, 2939–2948 (2010).

    Article  CAS  PubMed  Google Scholar 

  • Andrews, S. J. & Rothnagel, J. A. Emerging evidence for functional peptides encoded by short open reading frames. Nat. Rev. Genet. 15, 193–204 (2014).

    Article  CAS  PubMed  Google Scholar 

  • Ji, Z., Song, R., Regev, A. & Struhl, K. Many lncRNAs, 5′UTRs, and pseudogenes are translated and some are likely to express functional proteins. eLife 4, e08890 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  • Buhl, A. M. et al. Identification of a gene on chromosome 12q22 uniquely overexpressed in chronic lymphocytic leukemia. Blood 107, 2904–2911 (2006).

    Article  CAS  PubMed  Google Scholar 

  • Lin, B. et al. PART-1: a novel human prostate-specific, androgen-regulated gene that maps to chromosome 5q12. Cancer Res. 60, 858–863 (2000).

    CAS  PubMed  Google Scholar 

  • Pekarsky, Y., Rynditch, A., Wieser, R., Fonatsch, C. & Gardiner, K. Activation of a novel gene in 3q21 and identification of intergenic fusion transcripts with ecotropic viral insertion site I in leukemia. Cancer Res. 57, 3914–3919 (1997).

    CAS  PubMed  Google Scholar 

  • Kaushal, A. et al. A novel transcript from the KLKP1 gene is androgen regulated, down-regulated during prostate cancer progression and encodes the first non-serine protease identified from the human kallikrein gene locus. Prostate 68, 381–399 (2008).

    Article  CAS  PubMed  Google Scholar