TY - JOUR

T1 - Validating the Demethylating Effects of 5-aza-2'-deoxycytidine in Insects Requires a Whole-Genome Approach

AU - Cook, Nicola

AU - Parker, Darren J

AU - Tauber, Eran

AU - Pannebakker, Bart A

AU - Shuker, David M

PY - 2019/9

Y1 - 2019/9

N2 - 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.

AB - 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.

KW - Animals

KW - Azacitidine

KW - DNA Methylation

KW - Decitabine

KW - Epigenesis, Genetic

KW - Female

KW - Sex Ratio

KW - Wasps

U2 - 10.1086/704248

DO - 10.1086/704248

M3 - Article

C2 - 31553206

VL - 194

SP - 432

EP - 438

JO - American Naturalist

JF - American Naturalist

SN - 0003-0147

IS - 3

ER -