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Reversal of an ancient sex chromosome to an autosome in Drosophila


Although transitions of sex-determination mechanisms are frequent in species with homomorphic sex chromosomes1,2,3, heteromorphic sex chromosomes are thought to represent a terminal evolutionary stage owing to chromosome-specific adaptations such as dosage compensation or an accumulation of sex-specific mutations1,4. Here we show that an autosome of Drosophila, the dot chromosome, was ancestrally a differentiated X chromosome. We analyse the whole genome of true fruitflies (Tephritidae), flesh flies (Sarcophagidae) and soldier flies (Stratiomyidae) to show that genes located on the dot chromosome of Drosophila are X-linked in outgroup species, whereas Drosophila X-linked genes are autosomal. We date this chromosomal transition to early drosophilid evolution by sequencing the genome of other Drosophilidae. Our results reveal several puzzling aspects of Drosophila dot chromosome biology to be possible remnants of its former life as a sex chromosome, such as its minor feminizing role in sex determination5 or its targeting by a chromosome-specific regulatory mechanism6. We also show that patterns of biased gene expression of the dot chromosome during early embryogenesis, oogenesis and spermatogenesis resemble that of the current X chromosome. Thus, although sex chromosomes are not necessarily evolutionary end points and can revert back to an autosomal inheritance, the highly specialized genome architecture of this former X chromosome suggests that severe fitness costs must be overcome for such a turnover to occur.

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Figure 1: Sex chromosomes in higher Diptera revealed by genome analysis.
Figure 2: Properties of the dot chromosome in Drosophila melanogaster that resemble that of an X chromosome.
Figure 3: Gene expression in early embryos and adult gonads in outgroup Diptera species.
Figure 4: Turnover of sex chromosomes in Drosophila.

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  1. Bull, J. J. Evolution of Sex Determining Mechanisms (The Benjamin/Cummings Publishing Company, 1983)

    Google Scholar 

  2. Sarre, S. D., Ezaz, T. & Georges, A. Transitions between sex-determining systems in reptiles and amphibians. Annu. Rev. Genomics Hum. Genet. 12, 391–406 (2011)

    CAS  Article  Google Scholar 

  3. Pokorná, M. & Kratochvil, L. Phylogeny of sex-determining mechanisms in squamate reptiles: are sex chromosomes an evolutionary trap? Zool. J. Linn. Soc. 156, 168–183 (2009)

    Article  Google Scholar 

  4. Ohno, S. Sex Chromosomes and Sex-Linked Genes (Springer Verlag, 1967)

    Book  Google Scholar 

  5. Bridges, C. B. Sex in relation to chromosomes and genes. Am. Nat. 59, 127–137 (1925)

    Article  Google Scholar 

  6. Larsson, J., Chen, J. D., Rasheva, V., Rasmuson-Lestander, A. & Pirrotta, V. Painting of fourth, a chromosome-specific protein in Drosophila. Proc. Natl Acad. Sci. USA 98, 6273–6278 (2001)

    ADS  CAS  Article  Google Scholar 

  7. Bellott, D. W. & Page, D. C. Reconstructing the evolution of vertebrate sex chromosomes. Cold Spring Harb. Symp. Quant. Biol. 74, 345–353 (2009)

    CAS  Article  Google Scholar 

  8. Muller, H. J. in The New Systematics (ed. Huxley, J. ) 185–268 (Clarendon Press, 1940)

    Google Scholar 

  9. Holt, R. A. et al. The genome sequence of the malaria mosquito Anopheles gambiae. Science 298, 129–149 (2002)

    ADS  CAS  Article  Google Scholar 

  10. Cline, T. W. The Drosophila sex determination signal: how do flies count to two? Trends Genet. 9, 385–390 (1993)

    CAS  Article  Google Scholar 

  11. Zacharopoulou, A. Cytogenetic analysis of mitotic and salivary gland chromosomes in the Medfly Ceratitis capitata. Genome 29, 67–71 (1987)

    Article  Google Scholar 

  12. White, M. J. Cytological evidence on the phylogeny and classification of the Diptera. Evolution 3, 252–261 (1949)

    CAS  Article  Google Scholar 

  13. Vicoso, B. & Bachtrog, D. Lack of global dosage compensation in Schistosoma mansoni, a female-heterogametic parasite. Genome Biol. Evol. 3, 230–235 (2011)

    CAS  Article  Google Scholar 

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

    ADS  CAS  Article  Google Scholar 

  15. Lifschytz, E. & Lindsley, D. L. The role of X-chromosome inactivation during spermatogenesis. Proc. Natl Acad. Sci. USA 69, 182–186 (1972)

    ADS  CAS  Article  Google Scholar 

  16. Gelbart, M. E. & Kuroda, M. I. Drosophila dosage compensation: a complex voyage to the X chromosome. Development 136, 1399–1410 (2009)

    CAS  Article  Google Scholar 

  17. Larsson, J., Svensson, M. J., Stenberg, P. & Mäkitalo, M. Painting of fourth in genus Drosophila suggests autosome-specific gene regulation. Proc. Natl Acad. Sci. USA 101, 9728–9733 (2004)

    ADS  CAS  Article  Google Scholar 

  18. Riddle, N. C., Shaffer, C. D. & Elgin, S. C. A lot about a little dot – lessons learned from Drosophila melanogaster chromosome 4. Biochem. Cell Biol. 87, 229–241 (2009)

    CAS  Article  Google Scholar 

  19. Deng, X., Koya, S. K., Kong, Y. & Meller, V. H. Coordinated regulation of heterochromatic genes in Drosophila melanogaster males. Genetics 182, 481–491 (2009)

    CAS  Article  Google Scholar 

  20. Sánchez, L. Sex-determining mechanisms in insects. Int. J. Dev. Biol. 52, 837–856 (2008)

    Article  Google Scholar 

  21. Dübendorfer, A., Hediger, M., Burghardt, G. & Bopp, D. Musca domestica, a window on the evolution of sex-determining mechanisms in insects. Int. J. Dev. Biol. 46, 75–79 (2002)

    PubMed  Google Scholar 

  22. Traut, W. New Y chromosomes and early stages of sex chromosome differentiation: sex determination in Megaselia. J. Genet. 89, 307–313 (2010)

    Article  Google Scholar 

  23. Larracuente, A. M., Noor, M. A. & Clark, A. G. Translocation of Y-linked genes to the dot chromosome in Drosophila pseudoobscura. Mol. Biol. Evol. 27, 1612–1620 (2010)

    CAS  Article  Google Scholar 

  24. Gethmann, R. C. Crossing over in males of Higer Diptera (Brachycera). J. Hered. 79, 344–350 (1988)

    CAS  Article  Google Scholar 

  25. Zhou, Q. & Bachtrog, D. Sex-specific adaptation drives early sex chromosome evolution in Drosophila. Science 337, 341–345 (2012)

    ADS  CAS  Article  Google Scholar 

  26. Koerich, L. B., Wang, X., Clark, A. G. & Carvalho, A. B. Low conservation of gene content in the Drosophila Y chromosome. Nature 456, 949–951 (2008)

    ADS  CAS  Article  Google Scholar 

  27. Krivshenko, J. New evidence for the homology of the short euchromatic elements of the X and Y chromosomes of Drosophila busckii with the microchromosome of Drosophila melanogaster. Genetics 44, 1027–1040 (1959)

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Lott, S. E. et al. Noncanonical compensation of zygotic X transcription in early Drosophila melanogaster development revealed through single-embryo RNA-seq. PLoS Biol. 9, e1000590 (2011)

    CAS  Article  Google Scholar 

  29. Assis, R., Zhou, Q. & Bachtrog, D. Sex-biased transcriptome evolution in Drosophila. Genome Biol. Evol. 4, 1189–1200 (2012)

    Article  Google Scholar 

  30. 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  Google Scholar 

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

    CAS  Article  Google Scholar 

  32. Li, H. & Durbin, R. Fast and accurate long-read alignment with Burrows– Wheeler transform. Bioinformatics 26, 589–595 (2010)

    Article  Google Scholar 

  33. Langmead, B., Trapnell, C., Pop, M. & Salzberg, S. L. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol. 10, R25 (2009)

    Article  Google Scholar 

  34. Gabrieli, P. et al. Interchromosomal duplications on the Bactrocera oleae Y chromosome imply a distinct evolutionary origin of the sex chromosomes compared to Drosophila. PLoS ONE 6, e17747 (2011)

    ADS  CAS  Article  Google Scholar 

  35. Roy, V. et al. Evolution of the chromosomal location of rDNA genes in two Drosophila species subgroups: ananassae and melanogaster. Heredity 94, 388–395 (2005)

    CAS  Article  Google Scholar 

  36. Drosopoulou, E. et al. Sex chromosomes and associated rDNA form a heterochromatic network in the polytene nuclei of Bactrocera oleae (Diptera: Tephritidae). Genetica 140, 169–180 (2012)

    Article  Google Scholar 

  37. Parise-Maltempi, P. P. & Avancini, R. M. P. Cytogenetics of the neotropical flesh fly Pattonela intermutans (Diptera, Sarcophagidae). Genet. Mol. Biol. 23, 563–567 (2000)

    Article  Google Scholar 

  38. Parise-Maltempi, P. P. & Avancini, R. M. P. Comparative cytogenetic study in Muscidae flies. Braz. J. Biol. 67, 945–950 (2007)

    CAS  Article  Google Scholar 

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We thank S. Kunhi Purayil, I. Kadow, P. Mavragani, J. Larsson and U. Schmidt-Ott for samples, C. Zonneveld, L. Mazzon, D. Obbard, V. Aguiar, N. Gompel and J. Larsson for images, and Q. Zhou and Z. Walton for technical assistance. Funded by National Institutes of Health grants (R01GM076007 and R01GM093182) and a Packard Fellowship to D.B.

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B.V. and D.B. designed and performed the study, and wrote the manuscript.

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Correspondence to Doris Bachtrog.

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The authors declare no competing financial interests.

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All the DNA/RNA-sequencing reads generated in this study are deposited in the NCBI Short Reads Archive ( under bioprojects SRP021043, SRP021044 and SRP021047.

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Vicoso, B., Bachtrog, D. Reversal of an ancient sex chromosome to an autosome in Drosophila . Nature 499, 332–335 (2013).

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