The time is ripe for functional genomics: Can epigenetic changes mediate reproductive timing?

Populations are under strong selection to match reproductive timing with favourable environmental conditions. This becomes particularly important and challenging with increasing interannual environmental variability. Adjusting reproductive timing requires the ability to sense and interpret relevant environmental cues, while responding flexibly to their interannual variation. For instance, in seasonal species, reproductive timing is often dependent on photoperiod and temperature. Although many genes influencing the timing of reproduction have been identified, far less attention has been paid to the gene-regulatory cascades orchestrating these complex gene-environment interactions. In a From the Cover article in this issue of Molecular Ecology, Lindner, Laine, et al. (2021) addressed this knowledge gap by investigating the role of DNA methylation in mediating reproductive timing in the seasonally breeding great tit (Parus major). Using a clever blood sampling design, they investigated genome-wide DNA methylation changes following individual female birds across multiple reproductive stages. This approach revealed 10 candidate genes with a strong correlation between promoter methylation and reproductive status. Some of these genes are known to be involved in reproductive timing (e.g., MYLK-like or NR5A1), yet for others this function was previously unknown (Figure 1). Interestingly, NR5A1 is a key transcription factor, which may affect other genes that are part of the same regulatory network. The findings of Lindner, Laine, et al. (2021) provide a strong case for studying DNA methylation to uncover how gene-environment interactions influence important life-history traits, such as reproductive timing.