Digging for gold nuggets: uncovering novel candidate genes for variation in gastrointestinal nematode burden in a wild bird species

Abstract

The extent to which genotypic variation at a priori identified candidate genes can explain variation in complex phenotypes is a major debate in evolutionary biology. Whereas some high-profile genes such as the MHC or MC1R clearly do account for variation in ecologically relevant characters, many complex phenotypes such as response to parasite infection may well be underpinned by a large number of genes, each of small and effectively undetectable effect. Here, we characterize a suite of novel candidate genes for variation in gastrointestinal nematode (Trichostrongylus tenuis) burden among red grouse (Lagopus lagopus scotica) individuals across a network of moors in north-east Scotland. We test for associations between parasite load and genotypic variation in twelve genes previously identified to be differentially expressed in experimentally infected red grouse or genetically differentiated among red grouse populations with overall different parasite loads. These genes are associated with a broad physiological response including immune system processes. Based on individual-level generalized linear models, genotypic variants in nine genes were significantly associated with parasite load, with effect sizes accounting for differences of 514-666 worms per bird. All but one of these variants were synonymous or untranslated, suggesting that these may be linked to protein-coding variants or affect regulatory processes. In contrast, population-level analyses revealed few and inconsistent associations with parasite load, and little evidence of signatures of natural selection. We discuss the broader significance of these contrasting results in the context of the utility of population genomics and landscape genomics approaches in detecting adaptive genomic signatures.

Genome‐wide association and genome partitioning reveal novel genomic regions underlying variation in gastrointestinal nematode burden in a wild bird

“…These insights have been channelled into developing novel candidate genes for nematode susceptibility (Wenzel et al . ), which have been confirmed to explain variation in nematode burden among grouse individuals in a network of moors in northeast Scotland (Wenzel & Piertney ). In that same study system, DNA methylation patterns at specific genomic regions have also been linked to nematode burden, suggesting that parasites may affect epigenetic mechanisms impacting the regulations of specific genes (Wenzel & Piertney ).…”

“…Genome‐wide association identified five SNPs that were closely linked to novel genes putatively involved in multiple physiological processes beyond the immune system, consistent with the broad functions of previously identified genes using candidate gene approaches (Wenzel et al . ; Wenzel & Piertney ) and epigenetic DNA methylation analysis (Wenzel & Piertney ). Genome partitioning indicated moderate genome‐wide heritability of nematode burden, and highlighted that some chromosomes contain additive genotypic variants of individually small effects that represent disproportionate amounts of heritability.…”

“…; Wenzel et al . ; Wenzel & Piertney , ). Birds were either captured at night using lamping and netting techniques or collected following driven or walked‐up sporting shoots.…”

“…; Gossner et al . ; Wenzel & Piertney ). However, this strategy does not necessarily provide a robust understanding of the genetic basis of a phenotype because transcriptomic responses are context dependent and are not always linked to genotypic variation in homologues of different species (Orsini et al .…”

“…; Brown et al . ; Wenzel & Piertney ). A more robust genome‐scale understanding of genetic architecture can be gained by quantitative trait loci (QTL) mapping or genome‐wide association (GWA) analysis directly in the target species (Slate ; Hill ).…”