Discussion:
To our knowledge, ours is one of the first studies to consider how DNMT/TET expression could affect plasticity in free-living vertebrates (Sharma et al. 2018, Cardoso-JĂșnior et al. 2018), and only one other study (besides our own, see below) to our knowledge considered these genes in the context of range expansions (Fu et al. 2021). Given the strength of the patterns we found, it seems quite likely these enzymes played some role in the geographic distribution of this species, but both introduction history and especially temperature predictability had strong directional effects that ran counter to our predictions. Moreover, many other conspicuous factors were minimally predictive (e.g., sex, precipitation predictability), but for yet other factors, strong variation was also observed, namely heterogeneity in expression among tissues.
Variation in enzyme gene expression is not surprising among tissues. In the vertebrate nervous system, DNMT1 facilitates neuronal stability (Feng et al. 2010), underpins survival of new neurons (Noguchi et al. 2015), and regulates the differentiation of stem and progenitor cells (Fan et al. 2005). In the immune system, though, DNMT1 helps maintain multipotency of hematopoietic stem cells (HSCs) and lymphoid cell differentiation, and DNMT3 is critical for HSCs to maintain a self-renewal capacity (Suarez-Alvarez et al. 2012). DNMT1 also plays a strong role in thymopoiesis (i.e., circulating CD4+ and CD8+ T cell numbers) and T-cell derived immune pathology (Lee et al. 2001). TET2 prevents widespread gene enhancer hypermethylation, which can lead to leukemia (Rasmussen et al. 2015).
Differences in expression among countries where birds were captured, however, are harder to explain, as they largely run counter to our initial hypotheses. On the other hand, they are consistent with another study we conducted of house sparrows invading Senegal. There, we detected a similar pattern of DNMT differences among populations (Kilvitis et al. 2018). In that study, we asked whether hippocampal DNMT1 and 3 expression were higher in birds at the vanguard (city of Richard Toll) relative to birds from an intermediately-aged population (Saint Louis) and the site of introduction of the species in that specific brain region was expected to be an important mechanism whereby neurogenesis was regulated in coordination with glucocorticoid hormones (Liebl and Martin 2014, Liebl and Martin 2012, Martin et al. 2017). Whereas we detected a main effect of population age on DNMT1 expression (and an interesting relationship with glucocorticoid regulation), small sample sizes prevented us from determining whether expression increased or decreased towards the vanguard.