Balancing selection in Pattern Recognition Receptor signalling pathways is associated with gene function and pleiotropy in a wild rodent
Råberg, Lars et al. (2020), Balancing selection in Pattern Recognition Receptor signalling pathways is associated with gene function and pleiotropy in a wild rodent, Dryad, Dataset, https://doi.org/10.5061/dryad.2bvq83bms
Pathogen-mediated balancing selection is commonly considered to play an important role in the maintenance of genetic diversity, in particular in immune genes. However, there has not been any systematic analysis of what factors influence which immune genes are the targets of such selection. To address this, we here focus on Pattern Recognition Receptor (PRR) signalling pathways, which play a key role in innate immunity. We used whole-genome resequencing data from a population of bank voles (Myodes glareolus) to test for associations between balancing selection, pleiotropy and gene function in a set of 123 PRR signalling pathway genes. To investigate the effect of gene function, we compared genes encoding (i) receptors for microbial ligands vs downstream signalling proteins, and (ii) receptors recognizing components of microbial cell walls, flagella and capsids vs receptors recognizing features of microbial nucleic acids. Analyses based on the nucleotide diversity of full coding sequences showed that balancing selection primarily targeted receptor genes with a low degree of pleiotropy. Moreover, genes encoding receptors recognizing components of microbial cell walls etc were more important targets of balancing selection than receptors recognizing nucleic acids. Tests for localized signatures of balancing selection in coding and non-coding sequences showed that such signatures were mostly located in introns, and more evenly distributed among different functional categories of PRR pathway genes. The finding that signatures of balancing selection in full coding sequences primarily occur in receptor genes, in particular those encoding receptors for components of microbial cell walls etc, is consistent with the idea that coevolution between hosts and pathogens is an important cause of balancing selection on immune genes.