Signatures of positive selection in Toll-like receptor (TLR) genes in mammals

Helena Areal,Pedro J Esteves,Joana Abrantes

doi:10.1186/1471-2148-11-368

Abstract

BackgroundToll-like receptors (TLRs) are a major class of pattern recognition receptors (PRRs) expressed in the cell surface or membrane compartments of immune and non-immune cells. TLRs are encoded by a multigene family and represent the first line of defense against pathogens by detecting foreigner microbial molecular motifs, the pathogen-associated molecular patterns (PAMPs). TLRs are also important by triggering the adaptive immunity in vertebrates. They are characterized by the presence of leucine-rich repeats (LRRs) in the ectodomain, which are associated with the PAMPs recognition. The direct recognition of different pathogens by TLRs might result in different evolutionary adaptations important to understand the dynamics of the host-pathogen interplay. Ten mammal TLR genes, viral (TLR3, 7, 8, 9) and non-viral (TLR1-6, 10), were selected to identify signatures of positive selection that might have been imposed by interacting pathogens and to clarify if viral and non-viral TLRs might display different patterns of molecular evolution.ResultsBy using Maximum Likelihood approaches, evidence of positive selection was found in all the TLRs studied. The number of positively selected codons (PSC) ranged between 2-26 codons (0.25%-2.65%) with the non-viral TLR4 as the receptor with higher percentage of positively selected codons (2.65%), followed by the viral TLR8 (2.50%). The results indicated that viral and non-viral TLRs are similarly under positive selection. Almost all TLRs have at least one PSC located in the LRR ectodomain which underlies the importance of the pathogen recognition by this region.ConclusionsOur results are not in line with previous studies on primates and birds that identified more codons under positive selection in non-viral TLRs. This might be explained by the fact that both primates and birds are homogeneous groups probably being affected by only a restricted number of related viruses with equivalent motifs to be recognized. The analyses performed in this work encompassed a large number of species covering some of the most representative mammalian groups - Artiodactyla, Rodents, Carnivores, Lagomorphs and Primates - that are affected by different families of viruses. This might explain the role of adaptive evolution in shaping viral TLR genes.

Highlights

Toll-like receptors (TLRs) are a major class of pattern recognition receptors (PRRs) expressed in the cell surface or membrane compartments of immune and non-immune cells
Phylogenetic position and class of microbial compound that they recognize, vertebrate TLRs can be classified into six subfamilies: the TLR1 subfamily encompasses TLR1, 2, 6 and 10; the TLR9 subfamily includes TLR7, 8 and 9; TLR11, 12 and 13 constitute the subfamily TLR11 and TLR3, TLR4 and TLR5 each form a subfamily [6,7]
Signatures of positive selection Genes of the immune system, in particular those involved in the recognition of pathogens, and genes involved in the host-pathogen interaction have been shown to be highly prone to adaptive selection (e.g. [37,38])

Summary

Introduction

Toll-like receptors (TLRs) are a major class of pattern recognition receptors (PRRs) expressed in the cell surface or membrane compartments of immune and non-immune cells. TLRs are important by triggering the adaptive immunity in vertebrates They are characterized by the presence of leucine-rich repeats (LRRs) in the ectodomain, which are associated with the PAMPs recognition. Mutations or loss of these patterns can be lethal to the pathogens and are quite conserved [13] This means that a limited number of PRRs is needed to detect the presence of an infection [13]. Their main recognition molecules, the LRRs, are capped in the amino and carboxy termini by LRR-NT and LRRCT molecules, respectively [16,17], that stabilize the protein structure by protecting the hydrophobic core from exposure to solvent [18]. This is not the case for all species which further complicates the correct delimitation of each domain

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