Deleterious mutations vs. epigenetic mechanisms
How do deleterious mutations and epigenetics interplay?
While we know that both deleterious mutations and epigenetic variation contribute to fitness, little is known how the two interplay on a molecular level. The epigenome is affected by genetic factors, such as genetic variation and epigenetic regulator genes, and the two are therefore not independent of each other.
Earlier research has investigated this interplay by testing how DNA methylation relates to inbreeding depression. Interestingly, scientists found that inbreeding depression disappear when methylation was removed. But, we have a poor understanding how this mechanism operates on the level of the nucleotide.
Drawing on evidence from model organisms, my colleagues and I wrote an opinion piece on the hypothesized interplay between deleterious mutations and epigenetic mechanisms. The opinion piece is divided into three main hypotheses and sub-hypotheses. We hypothesise that epigenetic regulation may (i) be disrupted by deleterious mutations in non-coding regions and epigenetic regulator genes; (ii) buffer the expression of deleterious mutations; and (iii) contribute to the repair and purging of deleterious mutations.
Scientists have access to a wide variety of molecular and bioinformatic tools which enables eco-evolutionary molecular biologists to test our hypotheses with empirical data. This empirical evidence is critical because testing how epigenetic mechanisms influence the functional effects of mutations is vital for understanding fitness variation, guiding evolutionary predictions and informing conservation strategies.
This Opinion Piece has been accepted for publication in a Theme Issue for Phil Trans Royal Soc B and will soon become available under the DOI 10.1098/rstb.2025.0032.
Future directions
The hypotheses form a theoretical framework for molecular biologists including myself. In my postdoctoral position, I will test our proposed hypotheses using the black grouse study system.