Abstract
Selective pressure from pathogens is considered a key selective force driving the evolution of components of the immune system. Since single components of the immune system may interact with many pathogens, and single pathogens may be recognized by multiple components of the immune system, gaining a better understanding of the mechanisms of parasite-driven selection requires the study of multiple genes and pathogens. Toll-like receptors (TLRs) are a large gene family that code for antigen-presenting components of the innate immune response. In the present paper we characterize polymorphism and signatures of selection in seven TLRs in free-living bank voles Myodes glareolus. We report the first evidence of balancing selection in several TLR genes, supported by positive values of Fu and Li’s D* in TLR2 and TLR5, and positive values of Tajima’s D in LRR regions within TLR1 and TLR2. We further found significant associations between amino-acid alleles of TLR1 and TLR5 and susceptibility to infection with the blood pathogen Bartonella. Interestingly, selection patterns in TLRs presenting virus-derived motifs (TLR7 and TLR9) differed considerably from those interacting with bacterial PAMPs. In contrast to the highly variable TLRs presenting bacterial motifs, TLR7 and TLR9 had low polymorphism and displayed signatures of directional selection. These findings suggest different functional responses across the TLR gene family and highlight the complexity of parasite-driven selection.
Highlights
Selective pressure from pathogens is considered a key selective force driving the evolution of components of the immune system
Clinical studies have shown that polymorphism within Toll-like receptors (TLRs) genes, in the part of the molecule interacting with pathogen-associated molecular patterns (PAMP), affects susceptibility to diseases in humans – for instance, a single nucleotide polymorphism (SNP) in the TLR2 gene has been attributed to susceptibility to tuberculosis, cytomeglaovirus, and borreliosis, whereas SNPs associated with susceptibility to hepatitis C virus have been identified in TLR7
The number of segregating sites and the nucleotide diversity per site were much lower in TLR7 and in TLR9 than in other loci, and TLR7 had considerably lower haplotype diversity compared to other loci
Summary
Selective pressure from pathogens is considered a key selective force driving the evolution of components of the immune system. Since single components of the immune system may interact with many pathogens, and single pathogens may be recognized by multiple components of the immune system, gaining a better understanding of the mechanisms of parasite-driven selection requires the study of multiple genes and pathogens. In contrast to the highly variable TLRs presenting bacterial motifs, TLR7 and TLR9 had low polymorphism and displayed signatures of directional selection These findings suggest different functional responses across the TLR gene family and highlight the complexity of parasite-driven selection. Toll like receptors (TLRs) are the key component of the innate immunity They recognize pathogen-associated molecular patterns (PAMP) derived from microorganisms such as viruses, bacteria, protozoa, and fungi. Associations between TLR variants and susceptibility have recently been found in TLR2 and TLR44,7 in free living species
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