Analysis of sequence variability and protein domain architectures for bovine peptidoglycan recognition protein 1 and Toll-like receptors 2 and 6

AbstractThe mammalian Toll-like receptors (TLRs) recognize invading pathogens, thereafter provoking innate immune responses, whereas peptidoglycan recognition protein 1 (PGLYRP1) is directly microbicidal. The primary objective of this study was to characterize single-nucleotide polymorphisms (SNPs) and insertion-deletion polymorphisms (indels) within bovine TLR2, TLR6, and PGLYRP1, thereby facilitating future TLR signaling, association, and PGLYRP1 microbicidal assays relevant to bovine innate immunity. Comparative sequence analysis for 10 bovine breeds revealed 83 polymorphisms (82 SNPs, 1 indel), with 15 nonsynonymous SNPs located within predicted functional domains. Of the 83 polymorphisms detected, 72 (87%) are reported here for the first time. Several predicted amino acid replacements encoded by bovine TLR2 and TLR6, but not PGLYRP1, resulted in the confident prediction of protein domain alterations. Prediction and comparison of protein domain architectures for TLR2 and TLR6 revealed six regions of leucine-rich-repeat patterning that was conserved among multiple species. Collectively, differences in the patterns and frequencies of polymorphism were noted between bovine TLRs that predominantly recognize viral ligands (TLRs 3, 7, 8, 9) and those that recognize microbial and/or unknown ligands (TLRs 1, 2, 5, 6, 10)