Patterns of pathogen prevalence are, at least partially, the result of coevolutionary host-pathogen interactions. Thus, exploring the distribution of host genetic variation in relation to infection by a pathogen within and across populations can provide important insights into mechanisms of host defence and adaptation. Here we use a landscape genomics approach (Bayenv) in conjunction with genome-wide data (ddRADseq) to test for associations between avian malaria (Plasmodium) prevalence and host genetic variation across 13 populations of the island endemic Berthelot’s pipit (Anthus berthelotii). Considerable and consistent spatial heterogeneity in malaria prevalence was observed among populations over a period of 15 years. The prevalence of malaria infection was also strongly positively correlated with pox (Avipoxvirus) prevalence. Multiple host loci showed significant associations with malaria prevalence after controlling for genome-wide neutral genetic structure. These sites were located near to or within genes linked to metabolism, stress response, transcriptional regulation, complement activity and the inflammatory response, many previously implicated in vertebrate responses to malarial infection. Our findings identify diverse genes - not just limited to the immune system - that may be involved in host protection against malaria and suggests that spatially variable pathogen pressure may be an important evolutionary driver of genetic divergence among wild animal populations, such as Berthelot’s pipit. Further, our data indicate that spatio-temporal variation in multiple different pathogens (e.g., malaria and pox in this case) may have to be studied together to develop a more holistic understanding of host pathogen-mediated evolution.

Genomes retain evidence of the demographic history and evolutionary forces that have shaped populations. Across island systems, contemporary patterns of genetic diversity reflect complex population demography, including colonisation events, bottlenecks, gene flow and genetic drift. Here, we investigate whether island founder events have prolonged effects on genome-wide diversity and runs of homozygosity (ROH) distributions, using whole genome resequencing from six populations across three archipelagos of Berthelot’s pipit (Anthus berthelotii) - a passerine which has undergone island speciation relatively recently. Pairwise sequential Markovian coalescent (PSMC) analyses estimated divergence from its sister species approximately two million years ago. Results indicate that all Berthelot’s pipit populations had shared ancestry until approximately 50,000 years ago, when the Madeiran archipelago populations were founded, while the Selvagens were colonised within the last 8,000 years. We identify extensive long ROH (>1 Mb) in genomes in the most recently colonised populations of Madeira and Selvagens which have experienced sequential island founder events and population crashes. Population expansion within the last 100 years may have eroded long ROH in the Madeiran archipelago, resulting in a prevalence of short ROH (<1 Mb). Extensive long and short ROH in the Selvagens reflects strong recent inbreeding, small contemporary effective population size and past bottleneck effects, with as much as 37.7% of the autosomes comprised of ROH >250 kb in length. These findings highlight the importance of demographic history, as well as selection and genetic drift, in shaping contemporary patterns of genomic diversity across diverging populations.

Understanding the mechanisms and genes that enable animal populations to adapt to pathogens is important from an evolutionary, health and conservation perspective. Berthelot’s pipit (Anthus berthelotii) experiences extensive and consistent spatial heterogeneity in avian pox infection pressure across its range of island populations, thus providing an excellent system with which to examine how pathogen-mediated selection drives spatial variation in immunogenetic diversity. Here we test for evidence of genetic variation associated with avian pox at both an individual and population-level. At the individual level, we find no evidence that variation in MHC class I and TLR4 (both known to be important in recognising viral infection) was associated with pox infection within two separate populations. However, using genotype-environment association (Bayenv) in conjunction with genome-wide (ddRAD-seq) data, we detected strong associations between population-level avian pox prevalence and allele frequencies of single nucleotide polymorphisms (SNPs) at a number of sites across the genome. These sites were located within genes involved in cellular stress signalling and immune responses, many of which have previously been associated with responses to viral infection in humans and other animals. Consequently, our analyses provide evidence that pathogen-mediated selection has shaped genomic variation among relatively recently colonised island bird populations, and highlights the utility of genotype-environment associations for identifying candidate genes involved in adaption to local pathogen pressures.

A key step in understanding the genetic basis of different evolutionary outcomes (e.g., adaptation) is to determine the roles played by different mutation types. To do this we must simultaneously consider different mutation types in an evolutionary framework. Here we propose a research framework that directly utilizes the most important characteristics of mutations, their population genetic effects, to determine their relative evolutionary significance. We review known population genetic effects of different mutation types and show how these may be connected to different evolutionary outcomes. We provide examples of how to implement this framework and pinpoint areas where more data, theory and synthesis are needed. Linking experimental and theoretical approaches to examine different mutation types simultaneously is a critical step towards understanding their evolutionary significance.