Reply to Soley: DNA methylation marks are stably transferred across generations in honey bees

Soley (1) argues that our study (2) does not prove that “transgenerational [epigenetic] inheritance serv[es] an adaptive role in evolution” in honey bees. This view misrepresents our intent. Our main findings are that in honey bees 1) DNA methylation profiles are much more similar between fathers and daughters than between unrelated males and females of different generations and 2) DNA methylation profiles are conserved across somatic and germline tissues (2). We are agnostic as to whether DNA methylation marks are caused by environmental or genetic factors. Rather, we stress that DNA methylation patterns are conserved across generations.

Soley misrepresents our main findings by stating that “only a fraction of the methylated regions was considered to have been thus transferred to the following generation” (1), referring to “the proportion of methylated CpGs that were inherited specifically from fathers to daughters [being] between 18 and 29%.” These figures are correct, yet they only refer to a small portion of the methylome that has informative polymorphisms for which it is possible to ascertain parental origin. In fact, 85 ± 3% of DNA methylation sites have an identical status across generations (2).

Soley argues that sequence polymorphism is probably the key determinant of the DNA methylation state in honey bees (1). We concur, as already highlighted in some of our previous papers (3, 4).

Soley further questions the absence of epigenetic reprogramming in honey-bee embryos (1). We agree that our findings leave open the possibility that DNA methylation marks are erased and reapplied in a genotype-specific manner each generation. Yet, recent studies have clearly shown that there is no remodeling of DNA methylation during development in honey bees (5, 6). We thus think that epigenetic reprogramming is highly unlikely in honey bees, and probably in many other nonmammalian organisms (7).

Finally, we welcome Soley’s points on future directions needed to fully ascertain the presence of transgenerational epigenetic inheritance in bees (1), as we state in our own conclusions: “Whether [transgenerational epigenetic inheritance] processes are adaptive or able to influence macroevolution remains unclear.… It is thus more than ever necessary to uncover the molecular consequences of DNA methylation if we are to understand its evolutionary implications” (2).