Validating the demethylating effects of 5-aza-2′-deoxycytidine in insects requires a whole-genome approach: (A reply to ellers et al.)

Nicola Cook, Darren J. Parker, Eran Tauber, Bart A. Pannebakker, David M. Shuker

Research output: Contribution to journalLetterpeer-review


We previously demonstrated that treatment with the demethylating agent 5-aza-2-deoxycytidine (5-aza-dC) alters the offspring sex ratios produced by females of the parasitoid wasp Nasonia vitripennis. Females allocate offspring sex ratio in line with local mate competition theory, producing more or less female-biased sex ratios as the number of other females laying eggs on a patch varies, thereby reducing competition among their sons for mates. Interestingly, treatment with 5-aza-dC did not ablate the facultative sex allocation response. Instead, sex ratios became less female biased, a shift in the direction of the optimum sex ratio for paternally inherited alleles according to genomic conflict theory. This was the first (albeit indirect) experimental evidence for genomic conflict over sex allocation. In their comment, Ellers and colleagues assayed the effects of 5-aza-dC on DNA methylation in 10 Nasonia genes, finding no evidence of demethylation in these 10 genes, from which they conclude that 5-aza-dC has no demethylating capability in N. vitripennis. Quantifying the efficacy of 5-aza-dC in terms of demethylation is indeed crucial to in-depth interpretation of studies using 5-aza-dC to link phenotypes to epigenetic regulation. Here we outline the mode of action of 5-aza-dC and demonstrate that determining the efficacy of 5-aza-dC in insect systems requires a whole-genome approach.

Original languageEnglish
Pages (from-to)432-438
Number of pages7
JournalAmerican Naturalist
Issue number3
StatePublished - 1 Sep 2019

Bibliographical note

Funding Information:
First, we thank Mark Lammers and Jacintha Ellers for the collegiate and constructive engagement with our previous research and the editorial board for the opportunity to respond to their critique. Second, we thank Jade Green for assistance in the laboratory with practical work referred to in this article. We are also grateful to Matthew Arno and the Edinburgh Genomics team for their sequencing and downstream support with the data. This work was initiated as part of Natural Environment Research Council grant NE/J024481/1.

Publisher Copyright:
© 2019 by The University of Chicago. All rights reserved.


  • 5-aza-2-deoxycytidine
  • DNA methylation
  • Nasonia vitripennis
  • Sex ratio

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics


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