Balancing selection on the complement system of a wild rodent.

Background: Selection pressure exerted by pathogens can influence patterns of genetic diversity in the host. In the immune system especially, numerous genes encode proteins involved in antagonistic interactions with pathogens, paving the way for coevolution that results in increased genetic diversity as a consequence of balancing selection. The complement system is a key component of innate immunity. Many complement proteins interact directly with pathogens, either by recognising pathogen molecules for complement activation, or by serving as targets of pathogen immune evasion mechanisms. Complement genes can therefore be expected to be important targets of pathogen-mediated balancing selection, but analyses of such selection on this part of the immune system have been limited.

Results: Using a population sample of whole-genome resequencing data from wild bank voles (n = 31), we estimated the extent of genetic diversity and tested for signatures of balancing selection in multiple complement genes (n = 44). Complement genes showed higher values of standardised β (a statistic expected to be high under balancing selection) than the genome-wide average of protein coding genes. One complement gene, FCNA, a pattern recognition molecule that interacts directly with pathogens, was found to have a signature of balancing selection, as indicated by the Hudson-Kreitman-Aguadé test (HKA) test. Scans for localised signatures of balancing selection in this gene indicated that the target of balancing selection was found in exonic regions involved in ligand binding.

Conclusion: The present study adds to the growing evidence that balancing selection may be an important evolutionary force on components of the innate immune system. The identified target in the complement system typifies the expectation that balancing selection acts on genes encoding proteins involved in direct interactions with pathogens.