Stability of epigentic marks

In order to determine whether epigenetic marks play a relevant role in evolution, it is crucial to understand to which extent they are stably inherited across generations. While in sexually reproducing species the concept of generation is very straightforward, it is not the same in asexually reproducing species. Therefore, when not specified, we will refer to “stability” as the ability of an epigenetic mark to be inherited through meiosis in sexually reproducing species. Alternatively, when dealing with asexually reproducing species, we will consider epigenetics marks transmittable through mitosis as “stable” as well.

Histone modifications

Histone modifications were shown to be associated with stress memory and to be, in some cases, stably inherited through mitosis in plants, yeast and animals (Shido et al. 2005; Audergon et al. 2015). Nevertheless, they seem to revert back upon meiosis and not to be transgenerationally inherited by the offspring (Pecinka and Mittelsten Scheid 2012). This is consistent with the observation that the parental H3 histone, carrying several modifications related to differential transcription, is replaced during zygote development in Arabidopsis thaliana (Ingouff et al. 2010). Although these findings do not completely rule out the possibility that locus specific histone modifications could be copy-pasted to the zygote, this was never observed so far.

Considering these observations, histone modifications do not seem to be good candidates in playing a role in the evolution of sexually reproducing species as they are not transmissible through meiosis. Nevertheless, this could be different for asexually reproducing species which do not undergo meiosis (Castonguay and Angers 2012). More on histone modifications can be found in Chapter 8.

DNA methylation

There is evidence from both plants and animals that DNA methylation variation can be inherited through mitosis and, at least partially, also through meiosis (Cubas, Vincent and Coen 1999; Mittelsten Scheid, Afsar, and Paszkowski 2003; Rangwal et al. 2003; Rangwal et al. 2006; Vaughn et al. 2007; Bossdorf et al. 2008). Nevertheless, the extent and stability of DNA methylation heritability through meiosis remain elusive, mainly due to the many variables at stake. DNA methylation stability varies as a function of sequence context , genomic context genebodies, promotors, TEs … and other factors. To elaborate, DNA methylation is maintained, produced and removed by different molecular mechanisms in the three different sequence contexts. While methylation in the symmetric CG, and mostly also CHG, contexts can be maintained in a copy-paste manner during cell division, asymmetric CHH methylation can only be maintained through De novo methylation induced by the RNA directed DNA methylation machinery (Law and Jacobsen 2010). This results in CHH methylation being more prone to variation (Secco et al. 2015; Dubin et al. 2015). Moreover, different genomic elements genebodies, promoters, TEs … differ in their ability to maintain DNA methylation variation. For example, repetitive elements and TEs are kept heavily methylated by the RdDM pathway, while other elements like gene promoters are more likely to change their methylation status in different environmental conditions (Lämke and Bäuerle 2017). These and other variables result in DNA methylation in different positions being subjected to different degrees of resetting during meiosis. More details on the molecular machinery driving DNA methylation are in Chapter 9 “Small and non-coding RNA”.

When looking at the “origin” of DNA methylation variation from this perspective, we have to consider that while stochastic epimutations appear randomly in the genome (and therefore have the same chance of appearing in different genomic elements) environmentally induced DNA methylation is “intentionally” targeting regions in which it has a function such as promoters and other regulatory regions … (Secco et al. 2015). For this reason, these two origins of DNA methylation variation should be considered separately. Several stress memory experiments were carried out to test for the heritability of environmentally induced DNA methylation and the general trend is that induced variation reverts back to its original state after one or few generations (Secco et al. 2015; Lämke and Bäuerle 2017). Stochastic epimutations, on the other hand, can be studied using Mutation Accumulation Lines with one study showing that stochastic epimutations revert back at a quicker rate than genetic mutations, but can remain stable over several generations (Becker et al. 2011; Johannes and Schmitz 2018).