Cytokine gene polymorphism and parasite susceptibility in free-living rodents: importance of non-coding variants

Abstract

AbstractAssociations between genetic variants and susceptibility to infections have long been studied in free-living hosts to infer contemporary evolutionary forces shaping genetic polymorphisms of the immunity genes. Despite extensive studies of receptors, such as MHC or TLR, little is known about efferent arm of the immune system. Cytokines are signalling molecules that trigger and modulate the immune response, acting as a crucial link between innate and adaptive immunity. In the present study we investigated how genetic variation in cytokines affects susceptibility to parasitic diseases in bank voles. We focused on three cytokines: tumour necrosis factor (TNF), lymphotoxin alpha (LTα), and interferon beta (IFNβ1). Two SNPs in LTα and two in IFNβ1 significantly affected susceptibility to nematodes, and was of them was also associated with susceptibility to microbial pathogen Bartonella. All these variants displayed signatures of selection. One of the variants was synonymous, and one was located in an intron. Our study shows that cytokines are prone to parasite-driven selection, and non-coding variants may play an important role in susceptibility to infections in wild systems.