Avian Toll-like receptor allelic diversity far exceeds human polymorphism: an insight from domestic chicken breeds

Abstract

Immune genes show remarkable levels of adaptive variation shaped by pathogen-mediated selection. Compared to humans, however, population polymorphism in animals has been understudied. To provide an insight into immunogenetic diversity in birds, we sequenced complete protein-coding regions of all Toll-like receptor ( TLR) genes with direct orthology between mammals and birds ( TLR3, TLR4, TLR5 and TLR7) in 110 domestic chickens from 25 breeds and compared their variability with a corresponding human dataset. Chicken TLRs ( chTLRs) exhibit on average nine-times higher nucleotide diversity than human TLRs ( hTLRs). Increased potentially functional non-synonymous variability is found in chTLR ligand-binding ectodomains. While we identified seven sites in chTLRs under positive selection and found evidence for convergence between alleles, no selection or convergence was detected in hTLRs. Up to six-times more alleles were identified in fowl (70 chTLR4 alleles vs. 11 hTLR4 alleles). In chTLRs, high numbers of alleles are shared between the breeds and the allelic frequencies are more equal than in hTLRs. These differences may have an important impact on infectious disease resistance and host-parasite co-evolution. Though adaptation through high genetic variation is typical for acquired immunity (e.g. MHC), our results show striking levels of intraspecific polymorphism also in poultry innate immune receptors.