The hpRNA/RNAi pathway is essential to resolve intragenomic conflict in the Drosophila male germline Journal Article


Authors: Lin, C. J.; Hu, F.; Dubruille, R.; Vedanayagam, J.; Wen, J.; Smibert, P.; Loppin, B.; Lai, E. C.
Article Title: The hpRNA/RNAi pathway is essential to resolve intragenomic conflict in the Drosophila male germline
Abstract: Intragenomic conflicts are fueled by rapidly evolving selfish genetic elements, which induce selective pressures to innovate opposing repressive mechanisms. This is patently manifest in sex-ratio (SR) meiotic drive systems, in which distorter and suppressor factors bias and restore equal transmission of X and Y sperm. Here, we reveal that multiple SR suppressors in Drosophila simulans (Nmy and Tmy) encode related hairpin RNAs (hpRNAs), which generate endo-siRNAs that repress the paralogous distorters Dox and MDox. All components in this drive network are recently evolved and largely testis restricted. To connect SR hpRNA function to the RNAi pathway, we generated D. simulans null mutants of Dcr-2 and AGO2. Strikingly, these core RNAi knockouts massively derepress Dox and MDox and are in fact completely male sterile and exhibit highly defective spermatogenesis. Altogether, our data reveal how the adaptive capacity of hpRNAs is critically deployed to restrict selfish gonadal genetic systems that can exterminate a species. Lin and Hu et al. reveal a critical biological usage of RNAi in Drosophila simulans to tame meiotic drive systems. Multiple autosomal hairpin-siRNA loci are deployed to suppress X-encoded distorter loci that bias progeny sex ratio. These loci are rapidly evolving and testis restricted, and such intragenomic conflicts may fuel speciation. © 2018 Elsevier Inc.
Keywords: controlled study; genetics; nonhuman; phenotype; animal; meiosis; metabolism; animals; allele; gene targeting; microrna; embryo; germ cell; small interfering rna; rna, small interfering; gene locus; drosophila; rna interference; heterozygote; sex ratio; physiology; evolution, molecular; rna; germ cells; molecular evolution; histone; 5' untranslated region; quantitative analysis; amplicon; homozygote; genomics; x chromosome; dna sequence; drosophila melanogaster; rna structure; rna helicase; argonaute protein; drosophila proteins; rna helicases; testis; mutagenesis; spermatozoon; spermatozoa; female fertility; drosophila protein; ribonuclease iii; null allele; rna sequence; male fertility; y chromosome; rnai; open reading frame; sirna; spermatogenesis; germline mutation; dcr-2 protein, drosophila; inverted repeat; argonaute proteins; suppressor factor; male; female; priority journal; article; insect genome; satellite dna; crispr-cas9 system; drosophila simulans; hprna; intragenomic conflict; ago2 protein, drosophila; gene knockout; insect chromosome; introgression; rna hairpin
Journal Title: Developmental Cell
Volume: 46
Issue: 3
ISSN: 1534-5807
Publisher: Cell Press  
Date Published: 2018-08-06
Start Page: 316
End Page: 326.e5
Language: English
DOI: 10.1016/j.devcel.2018.07.004
PUBMED: 30086302
PROVIDER: scopus
PMCID: PMC6114144
DOI/URL:
Notes: Article -- Export Date: 4 September 2018 -- Source: Scopus
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MSK Authors
  1. Eric C Lai
    159 Lai
  2. Peter Smibert
    16 Smibert
  3. Jiayu Wen
    11 Wen
  4. Fuqu   Hu
    5 Hu
  5. Ching-Jung   Lin
    8 Lin