Analysis of substitution rates showed that TLR5 is evolving at different rates among mammalian groups

Ana Pinheiro,Joana Abrantes,Fabiana Neves,Ana Águeda-Pinto,José Melo-Ferreira,Pedro J Esteves

doi:10.1186/s12862-019-1547-4

Abstract

BackgroundToll-like receptors (TLRs) are the most widely studied innate immunity receptors responsible for recognition of invading pathogens. Among the TLR family, TLR5 is the only that senses and recognizes flagellin, the major protein of bacterial flagella. TLR5 has been reported to be under overall purifying selection in mammals, with a small proportion of codons under positive selection. However, the variation of substitution rates among major mammalian groups has been neglected. Here, we studied the evolution of TLR5 in mammals, comparing the substitution rates among groups.ResultsIn this study we analysed the TLR5 substitution rates in Euungulata, Carnivora, Chiroptera, Primata, Rodentia and Lagomorpha, groups. For that, Tajima’s relative rate test, Bayesian inference of evolutionary rates and genetic distances were estimated with CODEML’s branch model and RELAX. The combined results showed that in the Lagomorpha, Rodentia, Carnivora and Chiroptera lineages TLR5 is evolving at a higher substitution rate. The RELAX analysis further suggested a significant relaxation of selective pressures for the Lagomorpha (K = 0.22, p < 0.01), Rodentia (K = 0.58, p < 0.01) and Chiroptera (K = 0.65, p < 0.01) lineages and for the Carnivora ancestral branches (K = 0.13, p < 0.01).ConclusionsOur results show that the TLR5 substitution rate is not uniform among mammals. In fact, among the different mammal groups studied, the Lagomorpha, Rodentia, Carnivora and Chiroptera are evolving faster. This evolutionary pattern could be explained by 1) the acquisition of new functions of TLR5 in the groups with higher substitution rate, i.e. TLR5 neofunctionalization, 2) by the beginning of a TLR5 pseudogenization in these groups due to some redundancy between the TLRs genes, or 3) an arms race between TLR5 and species-specific parasites.

Highlights

Toll-like receptors (TLRs) are the most widely studied innate immunity receptors responsible for recognition of invading pathogens
TLR3, TLR7, TLR8, TLR9, TLR11, TLR12 and TLR13 are located in the endosomal membrane and recognize mostly viral nucleic acids and bacterial molecules and Toxoplasma gondii profiling like molecule
The observation that in the TLR5 phylogeny (Fig. 1) some mammalian groups, such as the Lagomorpha, Rodentia, Chiroptera and Carnivora, present longer branches when compared to Primata and Euungulata suggested that in the different mammalian groups, TLR5 is evolving at different paces

Summary

Introduction

Toll-like receptors (TLRs) are the most widely studied innate immunity receptors responsible for recognition of invading pathogens. The innate immunity receptors responsible for this recognition are collectively called pattern recognition receptors (PRRs). TLR1, TLR2, TLR5, TLR6 and TLR10 are located on the cell surface and recognize bacterial, fungal and parasite ligands. TLR4 locates both on the cell surface and endosome and recognizes bacterial and viral ligands (reviewed in [4]). Mammalian immune system genes are permanently engaged in a co-evolutionary arms race with their target pathogens and are expected to have fast evolutionary rates. Despite TLRs being evolutionary conserved proteins across vertebrates, patterns of positive selection have been described on these genes regions responsible for pathogen detection [5,6,7,8]

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