Corticosterone is correlated to mediators of neural plasticity and epigenetic potential in the hippocampus of Senegalese house sparrows (Passer domesticus).

Our previous research on range-expanding house sparrows in Kenya revealed that (i) range-edge birds released more corticosterone (CORT) in response to a stressor than range-core birds, ii) that range-edge birds were more exploratory than range-core birds, and that (iii) all birds exhibited extensive variation in genome-wide DNA methylation among individuals, regardless of their position along the range expansion. Within the hippocampus, mediators of neural plasticity such as brain-derived neurotrophic factor (BDNF), can influence and be influenced by CORT, hippocampus-associated behaviors and regulatory epigenetic modification enzymes. Here, we investigated whether individuals and populations colonizing a new geographic range, Senegal, vary in the expression of BDNF and DNA methyltransferases (DNMTs) within the hippocampus and the release of CORT in response to a stressor. DNMT expression is an important mediator of epigenetic potential, the propensity of a genome to capacitate phenotypic variation via mechanisms such as DNA methylation. We surveyed three populations across Senegal, predicting that hippocampal BDNF and DNMT expression would be highest at the range-edge, and that BDNF and DNMT would be inversely related to one another, but would each positively covary with CORT within individuals. We found a nonlinear relationship between CORT and BDNF expression within individuals. Moreover, we found that CORT positively covaried with DNMT1 expression in a more recently established population, while the reverse was true in the oldest population (i.e. at the range-core). Our study is among the first to explore whether and how variation in CORT regulation contributes to variation in mediators of neural plasticity and epigenetic potential within the hippocampus of a range-expanding vertebrate.

Costs of immunity and their role in the range expansion of the house sparrow in Kenya.

There are at least two reasons to study traits that mediate successful range expansions. First, dispersers will found new populations and thus impact the distribution and evolution of species. Second, organisms moving into new areas will influence the fate of resident communities, directly competing with or indirectly affecting residents by spreading non-native or spilling-back native parasites. The success of invaders in new areas is likely mediated by a counterbalancing of costly traits. In new areas where threats are comparatively rare, individuals that grow rapidly and breed prolifically should be at an advantage. High investment in defenses should thus be disfavored. In the present study, we compared the energetic, nutritional and collateral damage costs of an inflammatory response among Kenyan house sparrow (Passer domesticus) populations of different ages, asking whether costs were related to traits of individuals from three different capture sites. Kenya is among the world's most recent range expansions for this species, and we recently found that the expression of Toll-like receptors (TLRs), leukocyte receptors that instigate inflammatory responses when bound to microbial elements, was related to the range expansion across the country. Here, we found (contrary to our expectations) that energetic and nutritional costs of inflammation were higher, but damage costs were lower, in range-edge compared with core birds. Moreover, at the individual level, TLR-4 expression was negatively related to commodity costs (energy and a critical amino acid) of inflammation. Our data thus suggest that costs of inflammation, perhaps mediated by TLR expression, might mitigate successful range expansions.

Corticosterone regulation in house sparrows invading Senegal.

What traits help organisms expand their ranges? Several behavioral and life history traits have been identified, but physiological and especially endocrinological factors have been minimally considered. Here, we asked whether steroid hormonal responses to stressors might be important. Previously, we found that corticosterone (CORT) responses to a standard restraint stressor were stronger at a range edge than at the core of the recent house sparrow (Passer domesticus) invasion of Kenya. In related work in the same system, we found that various behaviors (exploratory activity, responses to novelty, etc.) that are affected by CORT in other systems varied among sparrow populations in a manner that would suggest that CORT regulation directly influenced colonization success; birds at the range edge were less averse to novelty and more exploratory than birds from the core. Here, we asked whether the pattern in CORT regulation we observed in Kenya was also detectable in the more recent (∼1970) and independent invasion of Senegal. We found, as in Kenya, that Senegalese range-edge birds mounted stronger CORT responses to restraint than core birds. We also found lower baseline CORT in range-edge than core Senegalese birds, but little evidence for effects of individual sex, body mass or body size on CORT. Follow-up work will be necessary to resolve whether CORT regulation in Senegal (and Kenya) actively facilitated colonization success, but our work implicates glucocorticoids as a mediator of range expansion success, making stress responses potentially useful biomarkers of invasion risk.

Covariation in stress and immune gene expression in a range expanding bird.

The enemy release hypothesis (ERH) posits that hosts encounter fewer infectious parasites when they arrive in new areas, so individuals that adjust their immune defenses most effectively should thrive and even expand the range of that species. An important aspect of vertebrate immune defense is inflammation, as it provides rapid defense against diverse parasites. Glucocorticoids (GCs) are integral to the regulation of inflammation, so here we investigated whether and how covariation in the expression of genes affecting the regulation of inflammation and GCs might have impacted the house sparrow (Passer domesticus) invasion of Kenya. Toll-like receptors 2 and 4 (TLRs) detect microbial threats and instigate inflammatory responses, whereas the glucocorticoid receptor (GR) is integral to resolving inflammation via both local and systemic pathways. As with a previous study on circulating leukocytes, we found that splenic TLR-4 and TLR-2 (the latter marginally non-significant) expression was higher in younger than older populations but only when differences in spleen size were considered; birds at the range edge had larger spleens. In regards to covariation, we found that TLR-2, TLR-4 and GR expression were closely inter-related within individuals, but covariation did not differ among populations. Subsequently, our data suggest that house sparrows are using variants of a common stress-immune regulatory mechanism to expand their Kenyan range.

Ecological epigenetics.

Biologists have assumed that heritable variation due to DNA sequence differences (i.e., genetic variation) allows populations of organisms to be both robust and adaptable to extreme environmental conditions. Natural selection acts on the variation among different genotypes and ultimately changes the genetic composition of the population. While there is compelling evidence about the importance of genetic polymorphisms, evidence is accumulating that epigenetic mechanisms (e.g., chromatin modifications, DNA methylation) can affect ecologically important traits, even in the absence of genetic variation. In this chapter, we review this evidence and discuss the consequences of epigenetic variation in natural populations. We begin by defining the term epigenetics, providing a brief overview of various epigenetic mechanisms, and noting the potential importance of epigenetics in the study of ecology. We continue with a review of the ecological epigenetics literature to demonstrate what is currently known about the amount and distribution of epigenetic variation in natural populations. Then, we consider the various ecological contexts in which epigenetics has proven particularly insightful and discuss the potential evolutionary consequences of epigenetic variation. Finally, we conclude with suggestions for future directions of ecological epigenetics research.

Epigenetic Potential in Native and Introduced Populations of House Sparrows (Passer domesticus).

Epigenetic potential, defined as the capacity for epigenetically-mediated phenotypic plasticity, may play an important role during range expansions. During range expansions, populations may encounter relatively novel challenges while experiencing lower genetic diversity. Phenotypic plasticity via epigenetic potential might be selectively advantageous at the time of initial introduction or during spread into new areas, enabling introduced organisms to cope rapidly with novel challenges. Here, we asked whether one form of epigenetic potential (i.e., the abundance of CpG sites) in three microbial surveillance genes: Toll-like receptors (TLRs) 1B (TLR1B), 2A (TLR2A), and 4 (TLR4) varied between native and introduced house sparrows (Passer domesticus). Using an opportunistic approach based on samples collected from sparrow populations around the world, we found that introduced birds had more CpG sites in TLR2A and TLR4, but not TLR1B, than native ones. Introduced birds also lost more CpG sites in TLR1B, gained more CpG sites in TLR2A, and lost fewer CpG sites in TLR4 compared to native birds. These results were not driven by differences in genetic diversity or population genetic structure, and many CpG sites fell within predicted transcription factor binding sites (TFBS), with losses and gains of CpG sites altering predicted TFBS. Although we lacked statistical power to conduct the most rigorous possible analyses, these results suggest that epigenetic potential may play a role in house sparrow range expansions, but additional work will be critical to elucidating how epigenetic potential affects gene expression and hence phenotypic plasticity at the individual, population, and species levels.

Epigenetic Potential as a Mechanism of Phenotypic Plasticity in Vertebrate Range Expansions.

SYNOPSIS: During range expansions, organisms are often exposed to multiple pressures, including novel enemies (i.e., predators, competitors and/or parasites) and unfamiliar or limited resources. Additionally, small propagule sizes at range edges can result in genetic founder effects and bottlenecks, which can affect phenotypic diversity and thus selection. Despite these obstacles, individuals in expanding populations often thrive at the periphery of a range, and this success may be mediated by phenotypic plasticity. Increasing evidence suggests that epigenetic mechanisms may underlie such plasticity because they allow for more rapid phenotypic responses to novel environments than are possible via the accumulation of genetic variation. Here, we review how molecular epigenetic mechanisms could facilitate plasticity in range-expanding organisms, emphasizing the roles of DNA methylation and other epigenetic marks in the physiological regulatory networks that drive whole-organism performance. We focus on the hypothalamic-pituitary-adrenal (HPA) axis, arguing that epigenetically-mediated plasticity in the regulation of glucocorticoids in particular might strongly impact range expansions. We hypothesize that novel environments release and/or select for epigenetic potential in HPA variation and hence organismal performance and ultimately fitness.

The context of host competence: a role for plasticity in host-parasite dynamics.

Even apparently similar hosts can respond differently to the same parasites. Some individuals or specific groups of individuals disproportionately affect disease dynamics. Understanding the sources of among-host heterogeneity in the ability to transmit parasites would improve disease management. A major source of host variation might be phenotypic plasticity - the tendency for phenotypes to change across different environments. Plasticity might be as important as, or even more important than, genetic change, especially in light of human modifications of the environment, because it can occur on a more rapid timescale than evolution. We argue that variation in phenotypic plasticity among and within species strongly contributes to epidemiological dynamics when parasites are shared among multiple hosts, which is often the case.

Ecological Epigenetics: Beyond MS-AFLP.

Ecological Epigenetics studies the relationship between epigenetic variation and ecologically relevant phenotypic variation. As molecular epigenetic mechanisms often control gene expression, even across generations, they may impact many evolutionary processes. Multiple molecular epigenetic mechanisms exist, but methylation of DNA so far has dominated the Ecological Epigenetic literature. There are several molecular techniques used to screen methylation of DNA; here, we focus on the most common technique, methylation-sensitive-AFLP (MS-AFLP), which is used to identify genome-wide methylation patterns. We review studies that used MS-AFLP to address ecological questions, that describe which taxa have been investigated, and that identify general trends in the field. We then discuss, noting the general themes, four studies across taxa that demonstrate characteristics that increase the inferences that can be made from MS-AFLP data; we suggest that future MS-AFLP studies should incorporate these methods and techniques. We then review the short-comings of MS-AFLP and suggest alternative techniques that might address some of these limitations. Finally, we make specific suggestions for future research on MS-AFLP and identify questions that are most compelling and tractable in the short term.