Evaluation of toll-like receptor 6 polymorphism Reveals Balancing Selection in Indian Bos indicus ccattle Sodhi et al.

Abstract

Toll-like receptors (TLRs) are key components of the innate immune system, responsible for recognizing pathogen-associated molecular patterns (PAMPs) and initiating early immune responses. Among these TLR6, a member of the TLR1 subfamily, plays a central role in detecting bacterial lipopeptides through heterodimerization with TLR2. Despite its immunological importance, information on genetic variation and evolutionary patterns of TLR6 in Indian Bos indicus cattle is limited. In this study, we characterized the genetic diversity, structural variation, and evolutionary relationships of the bovine TLR6 gene across multiple Bos indicus breeds. Comparative analysis with Bos taurus revealed 31 SNPs, of which 16 were non-synonymous and 13 were synonymous, distributed across all functional domains except the signal peptide region. Majority of amino acid substitutions were conservative in polarity, suggesting stabilizing selection maintaining structural integrity. Functional predictions identified few potentially damaging substitutions localized within the LRR domain, pointing towards possible effects on ligand binding and TLR2–TLR6 heterodimerization. Phylogenetic analysis clustered B. indicus TLR6 sequences closely with B. taurus, confirming strong sequence conservation within the Bos lineage. However, divergence within indicine breed and positively selected residues in the LRR ectodomain indicated adaptive diversification driven by pathogen-mediated selection. These findings substantiate the importance of TLR6 polymorphisms as potential molecular indicators of adaptive immunity in Bos indicus cattle.