Letter | Published:

doublesex is a mimicry supergene

Nature volume 507, pages 229232 (13 March 2014) | Download Citation

Abstract

One of the most striking examples of sexual dimorphism is sex-limited mimicry in butterflies, a phenomenon in which one sex—usually the female—mimics a toxic model species, whereas the other sex displays a different wing pattern1. Sex-limited mimicry is phylogenetically widespread in the swallowtail butterfly genus Papilio, in which it is often associated with female mimetic polymorphism1,2,3. In multiple polymorphic species, the entire wing pattern phenotype is controlled by a single Mendelian ‘supergene’4. Although theoretical work has explored the evolutionary dynamics of supergene mimicry5,6,7,8,9, there are almost no empirical data that address the critical issue of what a mimicry supergene actually is at a functional level. Using an integrative approach combining genetic and association mapping, transcriptome and genome sequencing, and gene expression analyses, we show that a single gene, doublesex, controls supergene mimicry in Papilio polytes. This is in contrast to the long-held view that supergenes are likely to be controlled by a tightly linked cluster of loci4. Analysis of gene expression and DNA sequence variation indicates that isoform expression differences contribute to the functional differences between dsx mimicry alleles, and protein sequence evolution may also have a role. Our results combine elements from different hypotheses for the identity of supergenes, showing that a single gene can switch the entire wing pattern among mimicry phenotypes but may require multiple, tightly linked mutations to do so.

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Accessions

GenBank/EMBL/DDBJ

Sequence Read Archive

References

  1. 1.

    & Diversity in mimicry: paradox or paradigm? Trends Ecol. Evol. 13, 461–466 (1998)

  2. 2.

    The diversity and evolution of batesian mimicry in Papilio swallowtail butterflies. Evolution 63, 2707–2716 (2009)

  3. 3.

    Female-limited mimetic polymorphism: a review of theories and a critique of sexual selection as balancing selection. Anim. Behav. 78, 1029–1036 (2009)

  4. 4.

    & Super-genes and mimicry. Heredity 14, 175–185 (1960)

  5. 5.

    & Theoretical genetics of Batesian mimicry II. Evolution of supergenes. J. Theor. Biol. 55, 305–324 (1975)

  6. 6.

    & Mimicry: the hunting of the supergene. Curr. Biol. 21, R846–R848 (2011)

  7. 7.

    The Genetical Theory of Natural Selection (Clarendon Press, 1930)

  8. 8.

    The evolution of mimicry: a problem in ecology and genetics. Cold Spring Harb. Symp. Quant. Biol. 24, 131–140 (1959)

  9. 9.

    in The Biology of Butterflies (eds & ) 141–161 (Academic, 1984)

  10. 10.

    Contributions to an insect fauna of the Amazon valley (Lepidoptera: Heliconidae). Trans. Linn. Soc. (Lond.) 23, 495–566 (1862)

  11. 11.

    The genetics of polymorphism in the Lepidoptera. Adv. Genet. 5, 43–87 (1953)

  12. 12.

    & Evolution of diversity in warning color and mimicry: Polymorphisms, shifting balance, and speciation. Annu. Rev. Ecol. Syst. 30, 201–233 (1999)

  13. 13.

    & The genetics of the mimetic butterfly Papilio polytes L. Phil. Trans. R. Soc. Lond. B 263, 431–458 (1972)

  14. 14.

    , & The genetics of the mimetic butterfly Papilio memnon L. Phil. Trans. R. Soc. Lond. B 254, 37–89 (1968)

  15. 15.

    et al. Chromosomal rearrangements maintain a polymorphic supergene controlling butterfly mimicry. Nature 477, 203–206 (2011)

  16. 16.

    & The selfish Segregation Distorter gene complex of Drosophila melanogaster. Genetics 192, 33–53 (2012)

  17. 17.

    & Self-incompatibility in plants. Annu. Rev. Plant Biol. 56, 467–489 (2005)

  18. 18.

    Developmental perspectives on evolution of butterfly mimicry. Bioscience 44, 148–157 (1994)

  19. 19.

    & Drosophila doublesex gene controls somatic sexual differentiation by producing alternatively spliced mRNAs encoding related sex-specific polypeptides. Cell 56, 997–1010 (1989)

  20. 20.

    & Genetic and molecular insights into the development and evolution of sexual dimorphism. Nature Rev. Genet. 10, 797–804 (2009)

  21. 21.

    Dmrt genes in the development and evolution of sexual dimorphism. Trends Genet. 28, 175–184 (2012)

  22. 22.

    , & Sex-specific splicing of the honeybee doublesex gene reveals 300 million years of evolution at the bottom of the insect sex-determination pathway. Genetics 177, 1733–1741 (2007)

  23. 23.

    , & Diversification of doublesex function underlies morph-, sex-, and species-specific development of beetle horns. Proc. Natl Acad. Sci. USA 109, 20526–20531 (2012)

  24. 24.

    , , , & Evolution of sex-specific traits through changes in HOX-dependent doublesex expression. PLoS Biol. 9, e1001131 (2011)

  25. 25.

    et al. The regulation and evolution of a genetic switch controlling sexually dimorphic traits in Drosophila. Cell 134, 610–623 (2008)

  26. 26.

    et al. Non-coding changes cause sex-specific wing size differences between closely related species of Nasonia. PLoS Genet. 6, e1000821 (2010)

  27. 27.

    & Elements of Evolutionary Genetics (Roberts & Co., 2010)

  28. 28.

    , & Chromosomal inversion polymorphisms and adaptation. Trends Ecol. Evol. 19, 482–488 (2004)

  29. 29.

    et al. Colour pattern specification in the Mocker swallowtail Papilio dardanus: the transcription factor invected is a candidate for the mimicry locus H. Proc. R. Soc. Lond. B 275, 1181–1188 (2008)

  30. 30.

    , & Genetics of mimicry in the tiger swallowtail butterflies, Papilio glaucus and P. canadensis (Lepidoptera: Papilionidae). Evolution 50, 222–236 (1996)

  31. 31.

    et al. SOAPdenovo2: an empirically improved memory-efficient short-read de novo assembler. Gigascience 1, 18 (2012)

  32. 32.

    & Fast gapped-read alignment with Bowtie 2. Nature Methods 9, 357–359 (2012)

  33. 33.

    et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20, 1297–1303 (2010)

  34. 34.

    et al. A framework for variation discovery and genotyping using next-generation DNA sequencing data. Nature Genet. 43, 491–498 (2011)

  35. 35.

    et al. The variant call format and VCFtools. Bioinformatics 27, 2156–2158 (2011)

  36. 36.

    & The control of the false discovery rate in multiple testing under dependency. Ann. Stat. 29, 1165–1188 (2001)

  37. 37.

    et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575 (2007)

  38. 38.

    , & A test of neutral molecular evolution based on nucleotide data. Genetics 116, 153–159 (1987)

  39. 39.

    , & Genome-wide characterization of adaptation and speciation in tiger swallowtail butterflies using de novo transcriptome assemblies. Genome Biol. Evol. 5, 1233–1245 (2013)

  40. 40.

    , , , & Pindel: a pattern growth approach to detect break points of large deletions and medium sized insertions from paired-end short reads. Bioinformatics 25, 2865–2871 (2009)

  41. 41.

    et al. Full-length transcriptome assembly from RNA-Seq data without a reference genome. Nature Biotechnol. 29, 644–652 (2011)

  42. 42.

    BLAT–the BLAST-like alignment tool. Genome Res. 12, 656–664 (2002)

  43. 43.

    & Protein structure prediction on the Web: a case study using the Phyre server. Nature Protocols 4, 363–371 (2009)

  44. 44.

    , & doublesex functions early and late in gustatory sense organ development. PLoS ONE 7, e51489 (2012)

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Acknowledgements

We thank W. Wang for sharing genome sequence data, C. Robinett for providing the Dsx-DM monoclonal antibody, and E. Westerman, S. Nallu, M. Zhang, G. Garcia and N. Pierce for assistance and discussion. This project was funded by National Science Foundation grant DEB-1316037 to M.R.K.

Author information

Author notes

    • K. Kunte
    •  & W. Zhang

    These authors contributed equally to this work.

Affiliations

  1. National Center for Biological Sciences, Tata Institute of Fundamental Research, Bengaluru 560065, India

    • K. Kunte
  2. Department of Ecology and Evolution, University of Chicago, Chicago, Illinois 60637, USA

    • W. Zhang
    • , A. Tenger-Trolander
    •  & M. R. Kronforst
  3. Committee on Evolutionary Biology, University of Chicago, Chicago, Illinois 60637, USA

    • D. H. Palmer
    •  & M. R. Kronforst
  4. Department of Ecology and Evolutionary Biology, Cornell University, Ithaca, New York 14853, USA

    • A. Martin
    •  & R. D. Reed
  5. Department of Biology, Boston University, Boston, Massachusetts 02215, USA

    • S. P. Mullen

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Contributions

K.K. conceived the project and helped design the study, reared mapping families and samples for gene expression analysis and genome sequencing, performed bulk-segregant analysis and RAD mapping, and contributed to drafting the manuscript. W.Z. generated the reference genome sequences and transcriptome assemblies, performed association mapping, GWAS analysis, HKA tests, structural variant detection and linkage disequilibrium analyses, analysis of protein structure and synonymous/non-synonymous calculations, and contributed to drafting the manuscript. A.T.-T. assisted with butterfly husbandry, performed fine mapping, cDNA sequencing and qRT–PCR analyses. D.H.P. performed qRT–PCR analyses. A.M. and R.D.R. performed Dsx immunohistochemistry. S.P.M. helped design the project and contributed to drafting the manuscript. M.R.K. designed and directed the project, analysed data and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to K. Kunte or M. R. Kronforst.

Sequence data are available from NCBI SRA (SRP035394) and GenBank (KJ150616KJ150623).

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DOI

https://doi.org/10.1038/nature13112

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