Molecular evolution of vertebrate Toll-like receptors: Evolutionary rate difference between their leucine-rich repeats and their TIR domains

Mikami, Takuma; Miyashita, Hiroki; Takatsuka, Shintaro; Kuroki, Yoshio; Matsushima, Norio

doi:10.1016/j.gene.2012.04.007

Cited by 76 publications

(70 citation statements)

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“…TLRs are receptor and signalling molecules that comprise two distinct domains. The extracellular leucinerich repeat (LRR) domain is responsible for recognizing and binding pathogen ligands and is subject to balancing selection, whereas the intracellular Toll interleukin-receptor (TIR) domain is involved in signalling to other components of the innate immune cascade and is subject to purifying selection (Barreiro et al 2009;Werling et al 2009;Alcaide and Edwards 2011;Tschirren et al 2011;Mikami et al 2012;Grueber et al 2014). These results demonstrate that selective forces can vary, even across small genomic scales, when the functional properties of innate immune genes differ.…”

Section: Introductionmentioning

confidence: 99%

The Evolution of Innate Immune Genes: Purifying and Balancing Selection on β-Defensins in Waterfowl

et al. 2016

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In disease dynamics, high immune gene diversity can confer a selective advantage to hosts in the face of a rapidly evolving and diverse pathogen fauna. This is supported empirically for genes involved in pathogen recognition and signalling. In contrast, effector genes involved in pathogen clearance may be more constrained. b-Defensins are innate immune effector genes; their main mode of action is via disruption of microbial membranes. Here, five b-defensin genes were characterized in mallards (Anas platyrhynchos) and other waterfowl; key reservoir species for many zoonotic diseases. All five genes showed remarkably low diversity at the individual-, population-, and species-level. Furthermore, there was widespread sharing of identical alleles across species divides. Thus, specific b-defensin alleles were maintained not only spatially but also over long temporal scales, with many amino acid residues being fixed across all species investigated. Purifying selection to maintain individual, highly efficacious alleles was the primary evolutionary driver of these genes in waterfowl. However, we also found evidence for balancing selection acting on the most recently duplicated b-defensin gene (AvBD3b). For this gene, we found that amino acid replacements were more likely to be radical changes, suggesting that duplication of b-defensin genes allows exploration of wider functional space. Structural conservation to maintain function appears to be crucial for avian b-defensin effector molecules, resulting in low tolerance for new allelic variants. This contrasts with other types of innate immune genes, such as receptor and signalling molecules, where balancing selection to maintain allelic diversity has been shown to be a strong evolutionary force.

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Section: Introductionmentioning

confidence: 99%

The Evolution of Innate Immune Genes: Purifying and Balancing Selection on β-Defensins in Waterfowl

et al. 2016

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“…Variability in the structure and binding features of TLR could significantly influence host resistance to diseases and vulnerability to autoimmune damage. TLR evolution has been intensively studied in vertebrates in general [4–6] and within the mammalian clade in particular [7–10]. In birds, although the number of studies on the evolution of TLR has steadily increased [11–13], there is still a very limited understanding of the functional significance of the putatively adaptive variability observed.…”

Section: Introductionmentioning

confidence: 99%

Protein evolution of Toll-like receptors 4, 5 and 7 within Galloanserae birds

2014

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BackgroundToll-like receptors (TLR) are essential activators of the innate part of the vertebrate immune system. In this study, we analysed the interspecific variability of three TLR (bacterial-sensing TLR4 and TLR5 and viral-sensing TLR7) within the Galloanserae bird clade, investigated their phylogeny, assessed their structural conservation and estimated site-specific selection pressures.ResultsPhysiochemical properties varied according to the TLR analysed, mainly with regards to the surface electrostatic potential distribution. The predicted ligand-binding features (mainly in TLR4 and TLR5) differed between the avian proteins and their fish and mammalian counterparts, but also varied within the Galloanserae birds. We identified 20 positively selected sites in the three TLR, among which several are topologically close to ligand-binding sites reported for mammalian and fish TLR. We described 26, 28 and 25 evolutionarily non-conservative sites in TLR4, TLR5 and TLR7, respectively. Thirteen of these sites in TLR4, and ten in TLR5 were located in functionally relevant regions. The variability appears to be functionally more conserved for viral-sensing TLR7 than for the bacterial-sensing TLR. Amino-acid positions 268, 270, 343, 383, 444 and 471 in TLR4 and 180, 183, 209, 216, 264, 342 and 379 in TLR5 are key candidates for further functional research.ConclusionsHost-pathogen co-evolution has a major effect on the features of host immune receptors. Our results suggest that avian and mammalian TLR may be differentially adapted to pathogen-derived ligand recognition. We have detected signatures of positive selection even within the Galloanserae lineage. To our knowledge, this is the first study to depict evolutionary pressures on Galloanserae TLR and to estimate the validity of current knowledge on TLR function (based on mammalian and chicken models) for non-model species of this clade.Electronic supplementary materialThe online version of this article (doi:10.1186/s12711-014-0072-6) contains supplementary material, which is available to authorized users.

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“…Only 4 and 7 non-synonymous SNPs were found in the human and porcine TLR3 gene, respectively (Ranjith-Kumar et al, 2007;Morozumi and Uenishi, 2009;Yang et al, 2011). Additionally, LRR domains of TLR3 and TLR7 show the lowest evolutionary rate from fishes to primates among all 15 TLRs identified thus far, except for TLR10 (Mikami et al, 2012). Together, this indicates that TLR3 has been subjected to severe selective pressures during evolution and any polymorphisms might therefore influence the receptor function.…”

Section: Discussionmentioning

confidence: 95%