Adaptive evolution of Toll-like receptor 5 in domesticated mammals

Sarah A Smith,Richard D Emes,Oliver C Jann,David Haig,George C Russell,Elizabeth J Glass,Dirk Werling

doi:10.1186/1471-2148-12-122

Abstract

BackgroundPrevious studies have proposed that mammalian toll like receptors (TLRs) have evolved under diversifying selection due to their role in pathogen detection. To determine if this is the case, we examined the extent of adaptive evolution in the TLR5 gene in both individual species and defined clades of the mammalia.ResultsIn support of previous studies, we find evidence of adaptive evolution of mammalian TLR5. However, we also show that TLR5 genes of domestic livestock have a concentration of single nucleotide polymorphisms suggesting a specific signature of adaptation. Using codon models of evolution we have identified a concentration of rapidly evolving codons within the TLR5 extracellular domain a site of interaction between host and the bacterial surface protein flagellin.ConclusionsThe results suggest that interactions between pathogen and host may be driving adaptive change in TLR5 by competition between species. In support of this, we have identified single nucleotide polymorphisms (SNP) in sheep and cattle TLR5 genes that are co-localised and co-incident with the predicted adaptive codons suggesting that adaptation in this region of the TLR5 gene is on-going in domestic species.

Highlights

Previous studies have proposed that mammalian toll like receptors (TLRs) have evolved under diversifying selection due to their role in pathogen detection
Evidence for adaptive evolution in mammalian TLR5 Positive diversifying selection acting on a gene can be inferred when the ratio of non-synonymous to synonymous substitution rates is greater than 1
Areal et al showed that positive selection is seen in a number of genes of the TLR family of proteins including multiple sites of positive selection in the TLR5 genes when using a subset of mammals [6]

Summary

Introduction

Previous studies have proposed that mammalian toll like receptors (TLRs) have evolved under diversifying selection due to their role in pathogen detection. To determine if this is the case, we examined the extent of adaptive evolution in the TLR5 gene in both individual species and defined clades of the mammalia. Toll-like receptors (TLRs) are type 1 transmembrane glycoproteins expressed on the cell surface and intracellular compartments of many cell types including epithelial cells and a variety of immune cells such as macrophages and dendritic cells. The TLR protein is comprised of three main regions: an extracellular patternrecognition receptor domain (ECD), a transmembrane region and an intracellular TIR signalling domain [3]. The ECD involved in pathogen detection is often variable [2]

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