Skip to main content

Thank you for visiting 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.

Satellite DNA-mediated diversification of a sex-ratio meiotic drive gene family in Drosophila


Sex chromosomes are susceptible to the evolution of selfish meiotic drive elements that bias transmission and distort progeny sex ratios. Conflict between such sex-ratio drivers and the rest of the genome can trigger evolutionary arms races resulting in genetically suppressed ‘cryptic’ drive systems. The Winters cryptic sex-ratio drive system of Drosophila simulans comprises a driver, Distorter on the X (Dox) and an autosomal suppressor, Not much yang, a retroduplicate of Dox that suppresses via production of endogenous small interfering RNAs (esiRNAs). Here we report that over 22 Dox-like (Dxl) sequences originated, amplified and diversified over the ~250,000-year history of the three closely related species, D. simulans, D. mauritiana and D. sechellia. The Dxl sequences encode a rapidly evolving family of protamines. Dxl copy numbers amplified by ectopic exchange among euchromatic islands of satellite DNAs on the X chromosome and separately spawned four esiRNA-producing suppressors on the autosomes. Our results reveal the genomic consequences of evolutionary arms races and highlight complex interactions among different classes of selfish DNAs.

Your institute does not have access to this article

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Physical distribution of known Dxl genes in D. simulans, D. mauritiana and D. sechellia.
Fig. 2: Inferred stepwise historical origins of Dox.
Fig. 3: Dxl genes encode a rapidly evolving protamine.
Fig. 4: Structural and sequence evolution among Dxl gene copies.
Fig. 5: Autosomal hpRNA suppressor loci in the D. simulans clade species.
Fig. 6: Species-specific small RNAs (≤22 nt) map to Dxl-matching hairpin regions of each species’ autosomal suppressors.

Data availability

All data used in our analyses are publicly available via the Sequence Read Archive. Data accessions are listed in Supplementary Tables 2 and 4.


  1. Sandler, L. & Novitski, E. Meiotic drive as an evolutionary force. Am. Nat. 91, 105–110 (1957).

    Google Scholar 

  2. Lindholm, A. K. et al. The ecology and evolutionary dynamics of meiotic drive. Trends Ecol. Evol. 31, 315–326 (2016).

    PubMed  Google Scholar 

  3. Lyttle, T. W. Segregation distorters. Annu. Rev. Genet. 25, 511–557 (1991).

    CAS  PubMed  Google Scholar 

  4. Lyttle, T. W. Cheaters sometimes prosper: distortion of Mendelian segregation by meiotic drive. Trends Genet. 9, 205–210 (1993).

    CAS  PubMed  Google Scholar 

  5. Presgraves, D. C. in Sperm Biology: An Evolutionary Perspective (eds Birkhead, T. R. et al.) Ch. 12, 472–506 (Elsevier Press, 2008).

  6. Hartl, D. L. Genetic dissection of segregation distortion. I. Suicide combinations of SD genes. Genetics 76, 477–486 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Charlesworth, B. & Hartl, D. L. Population dynamics of the segregation distorter polymorphism of Drosophila melanogaster. Genetics 89, 171–192 (1978).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Hamilton, W. D. Extraordinary sex ratios. Science 156, 477–488 (1967).

    CAS  PubMed  Google Scholar 

  9. 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 

  10. Frank, S. H. Divergence of meiotic drive-suppressors as an explanation for sex-biased hybrid sterility and inviability. Evolution 45, 262–267 (1991).

    PubMed  Google Scholar 

  11. Gershenson, S. A new sex ratio abnormality in Drosophila obscura. Genetics 13, 488–507 (1928).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Fisher, R. A. The Genetical Theory of Natural Selection (Oxford Univ. Press, 1930).

  13. Jaenike, J. Sex chromosome meiotic drive. Annu. Rev. Ecol. Syst. 32, 25–49 (2001).

    Google Scholar 

  14. Vaz, S. C. & Carvalho, A. B. Evolution of autosomal suppression of the sex-ratio trait in Drosophila. Genetics 166, 265–277 (2004).

    PubMed  PubMed Central  Google Scholar 

  15. Hall, D. W. Meiotic drive and sex chromosome cycling. Evolution 58, 925–931 (2004).

    PubMed  Google Scholar 

  16. Hartl, D. L. Modifier theory and meiotic drive. Theor. Popul. Biol. 7, 168–174 (1975).

    CAS  PubMed  Google Scholar 

  17. Thomson, G. J. & Feldman, M. W. Population genetics of modifiers of meiotic drive. II. Linkage modification in the Segregation Distorter system. Theor. Popul. Biol. 5, 155–162 (1974).

    CAS  PubMed  Google Scholar 

  18. Bastide, H., Gerard, P. R., Ogereau, D., Cazemajor, M. & Montchamp-Moreau, C. Local dynamics of a fast-evolving sex-ratio system in Drosophila simulans. Mol. Ecol. 22, 5352–5367 (2013).

    PubMed  Google Scholar 

  19. Haig, D. & Grafen, A. Genetic scrambling as a defence against meiotic drive. J. Theor. Biol. 153, 531–558 (1991).

    CAS  PubMed  Google Scholar 

  20. Burt, A. & Trivers, R. A. Genes in Conflict (Harvard Univ. Press, 2006).

  21. Meiklejohn, C. D. & Tao, Y. Genetic conflict and sex chromosome evolution. Trends Ecol. Evol. 25, 215–223 (2010).

    PubMed  Google Scholar 

  22. Bachtrog, D. The Y chromosome as a battleground for intragenomic conflict. Trends Genet. 36, 510–522 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Tao, Y. et al. A sex-ratio meiotic drive system in Drosophila simulans. II: An X-linked distorter. Public Libr. Sci. Biol. 5, e293 (2007).

    Google Scholar 

  24. Tao, Y., Masly, J. P., Araripe, L., Ke, Y. & Hartl, D. L. A sex-ratio meiotic drive system in Drosophila simulans. I: An autosomal suppressor. Public Libr. Sci. Biol. 5, e292 (2007).

    Google Scholar 

  25. Lin, C. J. et al. The hpRNA/RNAi pathway is essential to resolve intragenomic conflict in the Drosophila male germline. Dev. Cell 46, 316–326 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Kingan, S. B., Garrigan, D. & Hartl, D. L. Recurrent selection on the Winters sex-ratio genes in Drosophila simulans. Genetics 184, 253–265 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Meiklejohn, C. D. et al. Gene flow mediates the role of sex chromosome meiotic drive during complex speciation. eLife 7, e35468 (2018).

    PubMed  PubMed Central  Google Scholar 

  28. Nolte, V., Pandey, R. V., Kofler, R. & Schlotterer, C. Genome-wide patterns of natural variation reveal strong selective sweeps and ongoing genomic conflict in Drosophila mauritiana. Genome Res. 23, 99–110 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Garrigan, D., Kingan, S. B., Geneva, A. J., Vedanayagam, J. P. & Presgraves, D. C. Genome diversity and divergence in Drosophila mauritiana: multiple signatures of faster X evolution. Genome Biol. Evol. 6, 2444–2458 (2014).

    PubMed  PubMed Central  Google Scholar 

  30. Tao, Y., Hartl, D. L. & Laurie, C. C. Sex-ratio segregation distortion associated with reproductive isolation in Drosophila. Proc. Natl Acad. Sci. USA 98, 13183–13188 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Chakraborty, M. et al. Evolution of genome structure in the Drosophila simulans species complex. Genome Res. 31, 380–396 (2021).

    PubMed  PubMed Central  Google Scholar 

  32. Sproul, J. S. et al. Dynamic evolution of euchromatic satellites on the X chromosome in Drosophila melanogaster and the simulans clade. Mol. Biol. Evol. 37, 2241–2256 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Joshi, S. S. & Meller, V. H. Satellite repeats identify X chromatin for dosage compensation in Drosophila melanogaster males. Curr. Biol. 27, 1393–1402 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Garrigan, D. et al. Genome sequencing reveals complex speciation in the Drosophila simulans clade. Genome Res. 22, 1499–1511 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Kliman, R. M. et al. The population genetics of the origin and divergence of the Drosophila simulans complex species. Genetics 156, 1913–1931 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Miller, D., Brinkworth, M. & Iles, D. Paternal DNA packaging in spermatozoa: more than the sum of its parts? DNA, histones, protamines and epigenetics. Reproduction 139, 287–301 (2010).

    CAS  PubMed  Google Scholar 

  37. Gingell, L. F. & McLean, J. R. A protamine knockdown mimics the function of Sd in Drosophila melanogaster. G3 10, 2111–2115 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Larracuente, A. M. & Presgraves, D. C. The selfish Segregation Distorter complex of Drosophila melanogaster. Genetics 192, 33–53 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Wu, C.-I., Lyttle, T. W., Wu, M.-L. & Lin, G. F. Association between DNA satellite sequences and the responder of Segregation Distorter in D. melanogaster. Cell 54, 179–189 (1988).

    CAS  PubMed  Google Scholar 

  40. Thomas, J., Phillips, C. D., Baker, R. J. & Pritham, E. J. Rolling-circle transposons catalyze genomic innovation in a mammalian lineage. Genome Biol. Evol. 6, 2595–2610 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Hurst, L. D. Is Stellate a relict meiotic driver? Genetics 130, 229–230 (1992).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Cocquet, J. et al. The multicopy gene Sly represses the sex chromosomes in the male mouse germline after meiosis. PLoS Genet. 7, e1000244 (2009).

    Google Scholar 

  43. Kruger, A. N. et al. A neofunctionalized X-linked ampliconic gene family is essential for male fertility and equal sex ratio in mice. Curr. Biol. 29, 3699–3706 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Hu, W. et al. A large gene family in fission yeast encodes spore killers that subvert Mendel’s law. eLife 6, e26057 (2017).

    PubMed  PubMed Central  Google Scholar 

  45. Eickbush, M. T., Young, J. M. & Zanders, S. E. Killer meiotic drive and dynamic evolution of the wtf gene family. Mol. Biol. Evol. 36, 1201–1214 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Vogan, A. A. et al. Combinations of Spok genes create multiple meiotic drivers in Podospora. eLife 8, e46454 (2019).

    PubMed  PubMed Central  Google Scholar 

  47. Derome, N., Metayer, K., Montchamp-Moreau, C. & Veuille, M. Signature of selective sweep associated with the evolution of sex-ratio drive in Drosophila simulans. Genetics 1166, 1357–1366 (2004).

    Google Scholar 

  48. Presgraves, D. C., Gerard, P. R., Cherukuri, A. & Lyttle, T. W. Large-scale selective sweep among Segregation Distorter chromosomes in African populations of Drosophila melanogaster. PLoS Genet. 5, e1000463 (2009).

    PubMed  PubMed Central  Google Scholar 

  49. Nam, K. et al. Extreme selective sweeps independently targeted the X chromosomes of the great apes. Proc. Natl Acad. Sci. USA 112, 6413–6418 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Aravin, A. A. et al. Double-stranded RNA-mediated silencing of genomic tandem repeats and transposable elements in the D. melanogaster germline. Curr. Biol. 11, 1017–1027 (2001).

    CAS  PubMed  Google Scholar 

  51. Daugherty, M. D. & Zanders, S. E. Gene conversion generates evolutionary novelty that fuels genetic conflicts. Curr. Opin. Genet. Dev. 58–59, 49–54 (2019).

    PubMed  PubMed Central  Google Scholar 

  52. Beckmann, J. F., Sharma, G. D., Mendez, L., Chen, H. & Hochstrasser, M. The Wolbachia cytoplasmic incompatibility enzyme CidB targets nuclear import and protamine-histone exchange factors. eLife 8, e50026 (2019).

    PubMed  PubMed Central  Google Scholar 

Download references


This work was supported by funds from NIH grant no. R01 GM123194 and the University of Rochester to D.C.P. We thank J. J. Emerson, A. Larracuente, C. Meiklejohn, K. Montooth and J. Vedanayagam for early access to the PacBio-based genome assemblies. And we thank B. Navarro Dominguez and C. Meiklejohn for valuable feedback on the manuscript.

Author information

Authors and Affiliations



C.A.M. and D.C.P. conceived and designed the study. C.A.M. performed all analyses. C.A.M. and D.C.P. wrote the paper.

Corresponding author

Correspondence to Daven C. Presgraves.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature Ecology & Evolution thanks Aaron Vogan and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Extended data

Extended Data Fig. 1 Schematic alignment of inserted sat359 islands in X:9.4-10.4 Mb, colour-coded by putative sequence homology.

Segments of the same colour aligned vertically are high-confidence nucleotide alignments, whereas segments of different colour do not share sequence homology regardless of vertical alignment in the figure. One insertion into a sat359 island, the transposase-like sequence inserted into the D. sechellia Dxl-2 location, does not share sequence homology with any of the other loci, and has been omitted from this figure.

Extended Data Fig. 2 Alignment of the putative source material for Dxl genes found at approximate coordinates X:17.1 and X:17.2 Mb.

Segments of the same colour aligned vertically are high-confidence nucleotide alignments. At X:17.2, the three D. simulans clade species all have remnants of an insertion (total span = ~3 kb) that interrupts the CG8664 gene. This sequence, along with some of CG8664 and additional material, is alignable with insertion at the second position, X:17.1 Mb. Putative homology of the inserted sequence at both locations, along with CG8664, are colour-coded and the span of present-day Dxl homology is indicated.

Extended Data Fig. 3 Chromosomal distribution of sat359 islands in X:9.4-10.4 Mb region with all identified inserted sequence, including Dxl genes, in D. simulans, D. mauritiana, and D. sechellia.

Tick marks indicate locations of conserved sat359 islands, blue dots indicate protein-coding genes of interest in the region, and the different coloured squares represent the homologies of sequences inserted into sat359 islands (green=Dxl; purple=Ptpmeg2 fragment; brown=mkg-p retrotransposition; red=transposase-like sequence; yellow=cubn fragment; pink=CARPB intron fragments).

Extended Data Fig. 4 Evidence for transfer of Dxl material via a circular DNA intermediate molecule.

Dxl-12mau (green) is flanked by sat359 repeats (blue arrows) and by CARPB intronic sequence (boxes labelled A and B). These flanking sequence match sequences present in Dxl-10mau and Dxl-14mau, but the order of the two CARPB segments A and B differs from Dxl-12mau. The re-ordering of homologous sequences, as well as their intervening sequence, is consistent with a transfer of material via circular DNA intermediate.

Supplementary information

Supplementary Information

Supplementary text and Figs. 1–4.

Reporting Summary

Supplementary Tables

Supplementary Tables 1–4.

Supplementary Data 1

Alignment of inserted sat359 clusters.

Supplementary Data 2

Dxl protamines—positions 1–66, aligned with known protamines.

Supplementary Data 3

D. simulans r2.02, curated transcript set (‘base’ sequence set).

Supplementary Data 4

Consensus hairpin sequences of autosomal suppressors.

Supplementary Data 5

Species-specific consensus sequences, all Dxl-related sequence.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Muirhead, C.A., Presgraves, D.C. Satellite DNA-mediated diversification of a sex-ratio meiotic drive gene family in Drosophila. Nat Ecol Evol 5, 1604–1612 (2021).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

Further reading


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