Toll-Like Receptor 4 Polymorphism Impairing Lipopolysaccharide Signaling in Sus scrofa, and Its Restricted Distribution Among Japanese Wild Boar Populations

Toll-like receptor 4 (TLR4) responds to lipid A, the active moiety of lipopolysaccharide from Gram-negative bacteria, in cooperation with myeloid differentiation protein-2 and plays a vital role in innate immunity. Polymorphisms in TLR4 are associated with changes in susceptibility to various infectious diseases. We previously found seven amino acid polymorphisms in Sus scrofa TLR4. In this study, we showed by luciferase reporter assay that an alteration from cysteine to tryptophan at position 506 (C506W) caused loss of ability to induce nuclear factor-kappa B activation after lipid A stimulation. This polymorphism was found only in Japanese wild boar (JWB) populations of S. scrofa. Genotyping of TLR4 in different JWB populations revealed that C506W polymorphism was under pressure from purifying selection in a local population (Tajima's D = -0.98; p < 0.05). However, in another population, this polymorphism existed at a frequency such that homozygous animals with the W506 alleles seldom appeared. These findings suggest that the C506W polymorphism is under different types of pressure by natural selection between populations, which may reflect differences in residential pathogens or demographic factors.