House sparrows with high epigenetic potential in the Toll-like receptor 4 promoter are better able to resist a pathogenic Salmonella enterica infection

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. The CpG content of gene regulatory regions may therefore represent one form of epigenetic potential (EP), a genomic means to capacitate gene expression. 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 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 were better able to resist a pathogenic Salmonella enterica infection than sparrows with low EP. These results support the premise that high EP contributes to adaptation in novel environments.