High epigenetic potential protects songbirds against pathogenic Salmonella enterica infection

Abstract

Animals encounter many novel and unpredictable challenges when moving into new areas including pathogen exposure. Because effective immune defenses against such threats can be costly, plastic immune responses could be particularly advantageous, as such defenses can be engaged only when context warrants activation. DNA methylation is a key regulator of plasticity via its effects on gene expression. In vertebrates, DNA methylation occurs exclusively at CpG dinucleotides, and typically, high DNA methylation decreases gene expression, particularly when it occurs in promoters. The CpG content of gene regulatory regions may therefore represent one form of epigenetic potential (EP), a genomic means to capacitate gene expression and hence adaptive phenotypic plasticity. Non-native populations of house sparrows (Passer domesticus) - one of the world's most cosmopolitan species – have high EP in the promoter of a key microbial surveillance gene, Toll-like receptor 4 (TLR4), compared to native populations. We previously hypothesized that high EP may enable sparrows to balance the costs and benefits of inflammatory immune responses well, a trait critical to success in novel environments. In the present study, we found support for this hypothesis: house sparrows with high EP in TLR4 promoter were better able to resist a pathogenic Salmonella enterica infection than sparrows with low EP. These results support the idea that high EP contributes to invasion and perhaps adaptation in novel environments, but the mechanistic details whereby these organismal effects arise remain obscure.

Screening H3 Histone Acetylation in a Wild Bird, the House Sparrow (Passer Domesticus)

“…Partly, these population-level effects arise because individuals possess genomes with different dispositions to be epigenetically modified, a trait termed epigenetic potential ( Kilvitis et al. 2017 ; Sheldon et al. 2023 ).…”

“…Our goal was to facilitate investigations of histone acetylation and encourage the use of additional epigenetic markers beyond DNA methylation in ecological epigenetics. To do that we determined whether (1) histone acetylation can be measured in wild collected house sparrows using a commercially available assay developed for mammals, and (2) how variation in histone acetylation is related to a suit of characteristics in house sparrows that were experimentally exposed to Salmonella enterica ( Sheldon et al. 2023 ).…”

“…2023 ). We focused on two traits, epigenetic potential of the putative Toll Like Receptor-4 (TLR-4 ) promoter and TLR-4 expression, both are variable in the individuals screened and differ in response to infection ( Sheldon et al. 2023 ).…”

“…We measured histone acetylation in house sparrows that had been previously collected for a study on the response of individuals to S. enterica infection ( Sheldon et al. 2023 ).…”

“…These experimental samples provide us with the framework, in a controlled setting, to investigate relationships among epigenetic potential, acetylation and gene expression. Our primary focus was on epigenetic potential due to its importance in response to infection in Sheldon et al. (2023) and its relationship with TLR-4 expression ( Hanson et al.…”