Bioinformatics analysis of the structural and evolutionary characteristics for toll-like receptor 15

Wang, Jinlan; Zhang, Zheng; Chang, Fen; Yin, Deling

doi:10.7717/peerj.2079

Cited by 8 publications

(14 citation statements)

References 54 publications

(70 reference statements)

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“…2014 ; Vinkler et al. 2014 ; Wang, Zhang, Chang, et al. 2016 ) and studies that described the functionally relevant residues for TLR1 ( Jin et al.…”

Section: Methodsmentioning

confidence: 99%

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Toll-Like Receptor Evolution in Birds: Gene Duplication, Pseudogenization, and Diversifying Selection

Velová

Gutowska-Ding

Burt

et al. 2018

Molecular Biology and Evolution

140

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Toll-like receptors (TLRs) are key sensor molecules in vertebrates triggering initial phases of immune responses to pathogens. The avian TLR family typically consists of ten receptors, each adapted to distinct ligands. To understand the complex evolutionary history of each avian TLR, we analyzed all members of the TLR family in the whole genome assemblies and target sequence data of 63 bird species covering all major avian clades. Our results indicate that gene duplication events most probably occurred in TLR1 before synapsids diversified from sauropsids. Unlike mammals, ssRNA-recognizing TLR7 has duplicated independently in several avian taxa, while flagellin-sensing TLR5 has pseudogenized multiple times in bird phylogeny. Our analysis revealed stronger positive, diversifying selection acting in TLR5 and the three-domain TLRs (TLR10 [TLR1A], TLR1 [TLR1B], TLR2A, TLR2B, TLR4) that face the extracellular space and bind complex ligands than in single-domain TLR15 and endosomal TLRs (TLR3, TLR7, TLR21). In total, 84 out of 306 positively selected sites were predicted to harbor substitutions dramatically changing the amino acid physicochemical properties. Furthermore, 105 positively selected sites were located in the known functionally relevant TLR regions. We found evidence for convergent evolution acting between birds and mammals at 54 of these sites. Our comparative study provides a comprehensive insight into the evolution of avian TLR genetic variability. Besides describing the history of avian TLR gene gain and gene loss, we also identified candidate positions in the receptors that have been likely shaped by direct molecular host–pathogen coevolutionary interactions and most probably play key functional roles in birds.

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“…2014 ; Vinkler et al. 2014 ; Wang, Zhang, Chang, et al. 2016 ) and studies that described the functionally relevant residues for TLR1 ( Jin et al.…”

Section: Methodsmentioning

confidence: 99%

“…2008 ; Guan et al. 2010 ; Jang and Park 2014 ), TLR15 ( Wang, Zhang, Chang, et al. 2016 ), and TLR21 ( Keestra et al.…”

Section: Methodsmentioning

confidence: 99%

Toll-Like Receptor Evolution in Birds: Gene Duplication, Pseudogenization, and Diversifying Selection

Velová

Gutowska-Ding

Burt

et al. 2018

Molecular Biology and Evolution

140

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“…In the present work we provide evidence that (i) TLR15 is evolutionarily older than expected, (ii) tlr15 genes display species-specific codon usage, (iii) the tlr15 gene underwent evolutionary regression in most vertebrates including certain reptilian lineages, and (iv) that the activation of reptilian TLR15 by external proteases is a conserved feature that functionally distinguishes TLR15 from other TLR1 subfamily members. TLR15 was originally identified in chickens ( 17 ) and later studies found additional TLR15 orthologs in other avian and also four reptilian species (green anole lizard, Burmese python, Chinese alligator, and American alligator) ( 6 , 16 , 29 ). By combining phylogenetic and synteny analyses results, we identified TLR15 orthologs in even more reptilian species.…”

Section: Discussionmentioning

confidence: 99%

“…NF-κB reporter assays with TLR15-transfected cells clearly showed that the cloned reptilian TLR15 was proteolytically cleaved and activated by fungal proteases, as has previously been reported for chicken TLR15 ( 15 , 16 ). Chicken and reptilian TLR15 are predicted to share many structural characteristics including a highly conserved region in LRR11 which may be involved in the TLR15 activation process ( 29 ).…”

Section: Discussionmentioning

confidence: 99%

Evolutionary Regression and Species-Specific Codon Usage of TLR15

et al. 2018

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Toll-like receptors (TLRs) form an ancient family of innate immune receptors that detect microbial structures and activate the host immune response. Most subfamilies of TLRs (including TLR3, TLR5, and TLR7) are highly conserved among vertebrate species. In contrast, TLR15, a member of the TLR1 subfamily, appears to be unique to birds and reptiles. We investigated the functional evolution of TLR15. Phylogenetic and synteny analyses revealed putative TLR15 orthologs in bird species, several reptilian species and also in a shark species, pointing to an unprecedented date of origin of TLR15 as well as large scale reciprocal loss of this TLR in most other vertebrates. Cloning and functional analysis of TLR15 of the green anole lizard (Anolis carolinensis), salt water crocodile (Crocodylus porosus), American alligator (Alligator mississippiensis), and chicken (Gallus gallus) showed for all species TLR15 specific protease-induced activation of NF-κB, despite highly variable TLR15 protein expression levels. The variable TLR15 expression was consistent in both human and reptilian cells and could be attributed to species-specific differences in TLR15 codon usage. The species-specific codon bias was not or barely noted for more evolutionarily conserved TLRs (e.g., TLR3). Overall, our results indicate that TLR15 originates before the divergence of chondrichthyes fish and tetrapods and that TLR15 of both avian and reptilian species has a conserved function as protease activated receptor. The species-specific codon usage and large scale loss of TLR15 in most vertebrates suggest evolutionary regression of this ancient TLR.

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“…It appears that TLR15 is unique to birds and some reptilian species. TLR15 responds to in Salmonella enterica infections and is reported to have a unique auto‐activation mechanism . The avian TLR21 is an ortholog of the TLR21 proteins from teleost and amphibian species, and clusters into the TLR11 subfamily.…”

Section: Introductionmentioning

confidence: 99%

The evolutionary characteristics and structural biology of Gallus toll‐like receptor 21

Wang

Jiang

et al. 2017

J of Molecular Recognition

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Toll‐like receptors (TLRs) are an important part of the innate immune system, acting as a first line of defense against many invading pathogens. The ligand known to bind Gallus toll‐like receptor 21 (gTLR21) is the unmethylated cytosine phosphate guanine dideoxy nucleotide motif; however, the evolutionary characteristics and structural biology of gTLR21 are poorly elaborated. Our results suggest that gTLR21 is phylogenetically and evolutionarily related to the TLR11 family and is perhaps a close ortholog of the Mus TLR13. Structural biology of homology modeling of the gTLR21 ectodomain structure suggests that it has no Z‐loop like that seen in Mus TLR9. The cytosolic toll‐IL‐1 receptor region of gTLR21 contains a central 4‐stranded parallel β‐sheet (βA‐βD) surrounded by 5 α‐helices (αA‐αE) on both sides, a highly conserved structure also seen in other TLRs. Molecular docking analysis reveals that the gTLR21 ectodomain has the potential to distinguish between different ligands. Homodimer analysis results also suggest that Phe842 and Pro844 of the BB loop and Cys876 of the αC helix in gTLR21 are conserved in other cytosolic toll‐IL‐1 receptor domains of other TLRs and may contribute to the docking of homodimers. Our study on the evolutionary characteristics and structural biology of gTLR21 reveals that the molecule may have a broader role to play in innate immune system; however, further experimental validation is required to confirm our findings.

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Bioinformatics analysis of the structural and evolutionary characteristics for toll-like receptor 15

Cited by 8 publications

References 54 publications

Toll-Like Receptor Evolution in Birds: Gene Duplication, Pseudogenization, and Diversifying Selection

Toll-Like Receptor Evolution in Birds: Gene Duplication, Pseudogenization, and Diversifying Selection

Evolutionary Regression and Species-Specific Codon Usage of TLR15

The evolutionary characteristics and structural biology of Gallus toll‐like receptor 21

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