Novel ovine polymorphisms and adaptive evolution in mammalian TLR2 suggest existence of multiple pathogen binding regions

- We model adaptive evolution across TLR2 mammalian phylogeny.
- Sites of positive-selection suggest differential selection pressure across mammals.
- Novel SNPs identified in ovine TLR2 with predictions of functional relevance
- Two distinct pathogen binding regions are proposed on TLR2.

Toll-like receptors initiate inflammatory responses following the recognition of a wide repertoire of pathogens including bacteria, fungi, protozoa and viruses. They are composed of an extracellular leucine-rich repeat domain responsible for detecting pathogen-associated molecular patterns, a membrane spanning region and an intracellular Toll/Interleukin 1 receptor domain which invokes signal transduction. Toll-like receptor 2 is the most diverse of these receptors as it recognises infectious agents from a range of pathogenic groups. Over 1400 breeds of sheep exist worldwide that inhabit a diverse range of environments, which leads to the potential contact with a wide variety of pathogens likely detected by Toll-like receptor 2. In this study, we evaluated the extent of both long term evolutionary changes, across the mammalian phylogeny of the TLR2 gene, and recent divergence of this same gene in sheep breeds. Evolutionary analyses identified positive selective pressure across the mammalian phylogeny, and differential selection pressure within the artiodactyl and primate lineage. Finally, we identified localised positively-selected sites within two regions of the extracellular domain which suggest that multiple binding regions in TLR2 may be involved in pathogen detection. These results are consistent with the hypothesis that competition between host and pathogen is driving adaptation of Toll-like receptor 2 genes.