Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Genome Biol Evol
2014 Dec 04;71:81-95. doi: 10.1093/gbe/evu266.
Show Gene links
Show Anatomy links
Constraint and adaptation in newt toll-like receptor genes.
Babik W
,
Dudek K
,
Fijarczyk A
,
Pabijan M
,
Stuglik M
,
Szkotak R
,
Zieliński P
.
???displayArticle.abstract???
Acute die-offs of amphibian populations worldwide have been linked to the emergence of viral and fungal diseases. Inter and intraspecific immunogenetic differences may influence the outcome of infection. Toll-like receptors (TLRs) are an essential component of innate immunity and also prime acquired defenses. We report the first comprehensive assessment of TLR gene variation for urodele amphibians. The Lissotriton newt TLR repertoire includes representatives of 13 families and is compositionally most similar to that of the anuran Xenopus. Both ancient and recent gene duplications have occurred in urodeles, bringing the total number of TLR genes to at least 21. Purifying selection has predominated the evolution of newt TLRs in both long (∼70 Ma) and medium (∼18 Ma) timescales. However, we find evidence for both purifying and positive selection acting on TLRs in two recently diverged (2-5 Ma) allopatric evolutionary lineages (Lissotriton montandoni and L. vulgaris graecus). Overall, both forms of selection have been stronger in L. v. graecus, while constraint on most TLR genes in L. montandoni appears relaxed. The differences in selection regimes are unlikely to be biased by demographic effects because these were controlled by means of a historical demographic model derived from an independent data set of 62 loci. We infer that TLR genes undergo distinct trajectories of adaptive evolution in closely related amphibian lineages, highlight the potential of TLRs to capture the signatures of different assemblages of pathogenic microorganisms, and suggest differences between lineages in the relative roles of innate and acquired immunity.
Fig. 1.—. A Bayesian tree showing the relationships among vertebrate TLRs. Amphibian TLRs are color coded by species.
Fig. 2.—. Comparison of the domain structure between newt and frog TLRs. TLR19 is absent in Xenopus and zebrafish structure is provided instead; abbreviations of protein domains: LRR NT, Leucine-rich repeat, N-terminal; LRR, Leucine-rich repeat; LRR CT, LRR C-terminal.
Fig. 3.—. The distribution of fitness effects of new mutations in 11 Lissotriton TLR genes.
Fig. 4.—. Nucleotide diversity and Tajima’s D in population data sets; Lm, Lissotriton montandoni, Lvg, L. vulgaris graecus; π, overall, πS, synonymous and πN, nonsynonymous nucleotide diversity; D, overall, DS, synonymous and DN, nonsynonymous Tajima’s D.
Abdullayev,
A reference transcriptome and inferred proteome for the salamander Notophthalmus viridescens.
2013, Pubmed
Abdullayev,
A reference transcriptome and inferred proteome for the salamander Notophthalmus viridescens.
2013,
Pubmed
Akira,
Pathogen recognition and innate immunity.
2006,
Pubmed
Alcaide,
Molecular evolution of the toll-like receptor multigene family in birds.
2011,
Pubmed
Andersen-Nissen,
Evasion of Toll-like receptor 5 by flagellated bacteria.
2005,
Pubmed
Areal,
Signatures of positive selection in Toll-like receptor (TLR) genes in mammals.
2011,
Pubmed
Babik,
Phylogeography of two European newt species--discordance between mtDNA and morphology.
2005,
Pubmed
Barreiro,
Evolutionary dynamics of human Toll-like receptors and their different contributions to host defense.
2009,
Pubmed
Bauer,
Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition.
2001,
Pubmed
Boller,
Innate immunity in plants: an arms race between pattern recognition receptors in plants and effectors in microbial pathogens.
2009,
Pubmed
Chen,
Evidence for positive selection in the TLR9 gene of teleosts.
2008,
Pubmed
Cheng,
Coincident mass extirpation of neotropical amphibians with the emergence of the infectious fungal pathogen Batrachochytrium dendrobatidis.
2011,
Pubmed
Choi,
Predicting the functional effect of amino acid substitutions and indels.
2012,
Pubmed
Darriba,
ProtTest 3: fast selection of best-fit models of protein evolution.
2011,
Pubmed
Downing,
The differential evolutionary dynamics of avian cytokine and TLR gene classes.
2010,
Pubmed
Eilertson,
SnIPRE: selection inference using a Poisson random effects model.
2012,
Pubmed
Ferrer-Admetlla,
Balancing selection is the main force shaping the evolution of innate immunity genes.
2008,
Pubmed
Fisher,
Emerging fungal threats to animal, plant and ecosystem health.
2012,
Pubmed
Gentleman,
Bioconductor: open software development for computational biology and bioinformatics.
2004,
Pubmed
Grabherr,
Full-length transcriptome assembly from RNA-Seq data without a reference genome.
2011,
Pubmed
Grueber,
Episodic positive selection in the evolution of avian toll-like receptor innate immunity genes.
2014,
Pubmed
Grueber,
Variation at innate immunity Toll-like receptor genes in a bottlenecked population of a New Zealand robin.
2012,
Pubmed
Hansen,
Sensing disease and danger: a survey of vertebrate PRRs and their origins.
2011,
Pubmed
Huang,
Molecular evolution of the vertebrate TLR1 gene family--a complex history of gene duplication, gene conversion, positive selection and co-evolution.
2011,
Pubmed
Hudson,
Generating samples under a Wright-Fisher neutral model of genetic variation.
2002,
Pubmed
Ingvarsson,
Population subdivision and the Hudson-Kreitman-Aguade test: testing for deviations from the neutral model in organelle genomes.
2004,
Pubmed
Ishii,
Phylogenetic and expression analysis of amphibian Xenopus Toll-like receptors.
2007,
Pubmed
,
Xenbase
Iwasaki,
Regulation of adaptive immunity by the innate immune system.
2010,
Pubmed
Kanwal,
Comparative studies of Toll-like receptor signalling using zebrafish.
2014,
Pubmed
Katoh,
MAFFT: a novel method for rapid multiple sequence alignment based on fast Fourier transform.
2002,
Pubmed
Kawai,
The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors.
2010,
Pubmed
Kawai,
Toll-like receptors and their crosstalk with other innate receptors in infection and immunity.
2011,
Pubmed
Keestra,
Unique features of chicken Toll-like receptors.
2013,
Pubmed
Koblansky,
Recognition of profilin by Toll-like receptor 12 is critical for host resistance to Toxoplasma gondii.
2013,
Pubmed
Langmead,
Ultrafast and memory-efficient alignment of short DNA sequences to the human genome.
2009,
Pubmed
Letunic,
SMART 7: recent updates to the protein domain annotation resource.
2012,
Pubmed
Li,
RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome.
2011,
Pubmed
Librado,
DnaSP v5: a software for comprehensive analysis of DNA polymorphism data.
2009,
Pubmed
Luther,
Toll-like receptors: Recent advances, open questions and implications for aspergillosis control.
2006,
Pubmed
Martel,
Wildlife disease. Recent introduction of a chytrid fungus endangers Western Palearctic salamanders.
2014,
Pubmed
Matsuo,
Teleost TLR22 recognizes RNA duplex to induce IFN and protect cells from birnaviruses.
2008,
Pubmed
Medzhitov,
Toll-like receptors and innate immunity.
2001,
Pubmed
Mikami,
Molecular evolution of vertebrate Toll-like receptors: evolutionary rate difference between their leucine-rich repeats and their TIR domains.
2012,
Pubmed
Mukherjee,
Signatures of natural selection are not uniform across genes of innate immune system, but purifying selection is the dominant signature.
2009,
Pubmed
Mukherjee,
Global footprints of purifying selection on Toll-like receptor genes primarily associated with response to bacterial infections in humans.
2014,
Pubmed
Muñoz,
Molecular cloning, phylogenetic analysis and functional characterization of soluble Toll-like receptor 5 in gilthead seabream, Sparus aurata.
2013,
Pubmed
Nadachowska,
Divergence in the face of gene flow: the case of two newts (amphibia: salamandridae).
2009,
Pubmed
Nadachowska-Brzyska,
Interspecific hybridization increases MHC class II diversity in two sister species of newts.
2012,
Pubmed
Netea,
Genetic variation in Toll-like receptors and disease susceptibility.
2012,
Pubmed
Nikolaeva,
Frog urinary bladder epithelial cells express TLR4 and respond to bacterial LPS by increase of iNOS expression and L-arginine uptake.
2012,
Pubmed
Oldenburg,
TLR13 recognizes bacterial 23S rRNA devoid of erythromycin resistance-forming modification.
2012,
Pubmed
Oshiumi,
Pan-vertebrate toll-like receptors during evolution.
2008,
Pubmed
Palermo,
Toll-like receptor 4 genetic diversity among pig populations.
2009,
Pubmed
Palti,
Toll-like receptors in bony fish: from genomics to function.
2011,
Pubmed
Piertney,
The evolutionary ecology of the major histocompatibility complex.
2006,
Pubmed
Pietretti,
Identification and functional characterization of nonmammalian Toll-like receptor 20.
2014,
Pubmed
Pietretti,
Ligand specificities of Toll-like receptors in fish: indications from infection studies.
2014,
Pubmed
Quach,
Different selective pressures shape the evolution of Toll-like receptors in human and African great ape populations.
2013,
Pubmed
Quiniou,
Comprehensive survey and genomic characterization of Toll-like receptors (TLRs) in channel catfish, Ictalurus punctatus: identification of novel fish TLRs.
2013,
Pubmed
Quintana-Murci,
Population genetic tools for dissecting innate immunity in humans.
2013,
Pubmed
Rauta,
Toll-like receptors (TLRs) in aquatic animals: signaling pathways, expressions and immune responses.
2014,
Pubmed
Rigby,
RNA:DNA hybrids are a novel molecular pattern sensed by TLR9.
2014,
Pubmed
Roach,
The evolution of vertebrate Toll-like receptors.
2005,
Pubmed
Robinson,
edgeR: a Bioconductor package for differential expression analysis of digital gene expression data.
2010,
Pubmed
Roeder,
Toll-like receptors as key mediators in innate antifungal immunity.
2004,
Pubmed
Roelants,
Global patterns of diversification in the history of modern amphibians.
2007,
Pubmed
Ronquist,
MrBayes 3: Bayesian phylogenetic inference under mixed models.
2003,
Pubmed
Sackton,
Dynamic evolution of the innate immune system in Drosophila.
2007,
Pubmed
Savage,
MHC genotypes associate with resistance to a frog-killing fungus.
2011,
Pubmed
Star,
The genome sequence of Atlantic cod reveals a unique immune system.
2011,
Pubmed
Stephens,
A comparison of bayesian methods for haplotype reconstruction from population genotype data.
2003,
Pubmed
Stephens,
A new statistical method for haplotype reconstruction from population data.
2001,
Pubmed
Städler,
The impact of sampling schemes on the site frequency spectrum in nonequilibrium subdivided populations.
2009,
Pubmed
Sundaram,
Diversification of the expanded teleost-specific toll-like receptor family in Atlantic cod, Gadus morhua.
2012,
Pubmed
Takeda,
Toll-like receptors.
2003,
Pubmed
Tamura,
MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods.
2011,
Pubmed
Temperley,
Evolution of the chicken Toll-like receptor gene family: a story of gene gain and gene loss.
2008,
Pubmed
Tiffin,
Molecular evolution of plant immune system genes.
2006,
Pubmed
Tschirren,
Contrasting patterns of diversity and population differentiation at the innate immunity gene toll-like receptor 2 (TLR2) in two sympatric rodent species.
2012,
Pubmed
Tschirren,
Signatures of selection acting on the innate immunity gene Toll-like receptor 2 (TLR2) during the evolutionary history of rodents.
2011,
Pubmed
Tschirren,
Polymorphisms at the innate immune receptor TLR2 are associated with Borrelia infection in a wild rodent population.
2013,
Pubmed
Tsujita,
Sensing bacterial flagellin by membrane and soluble orthologs of Toll-like receptor 5 in rainbow trout (Onchorhynchus mikiss).
2004,
Pubmed
Wakeley,
Gene genealogies in a metapopulation.
2001,
Pubmed
Wakeley,
Metapopulation models for historical inference.
2004,
Pubmed
Wakeley,
Nonequilibrium migration in human history.
1999,
Pubmed
Werling,
Variation matters: TLR structure and species-specific pathogen recognition.
2009,
Pubmed
Wilson,
A population genetics-phylogenetics approach to inferring natural selection in coding sequences.
2011,
Pubmed
Wlasiuk,
Adaptation and constraint at Toll-like receptors in primates.
2010,
Pubmed
Wlasiuk,
A history of recurrent positive selection at the toll-like receptor 5 in primates.
2009,
Pubmed
Wright,
The HKA test revisited: a maximum-likelihood-ratio test of the standard neutral model.
2004,
Pubmed
Yang,
PAML 4: phylogenetic analysis by maximum likelihood.
2007,
Pubmed
Yarovinsky,
Innate immunity to Toxoplasma gondii infection.
2014,
Pubmed
Yeh,
Toll-like receptor 9 and 21 have different ligand recognition profiles and cooperatively mediate activity of CpG-oligodeoxynucleotides in zebrafish.
2013,
Pubmed
Zhao,
Comprehensive transcriptome profiling and functional analysis of the frog (Bombina maxima) immune system.
2014,
Pubmed
Zhu,
Evolutionary analysis of TLR9 genes reveals the positive selection of extant teleosts in Perciformes.
2013,
Pubmed
Zieliński,
Development, validation and high-throughput analysis of sequence markers in nonmodel species.
2014,
Pubmed
Zieliński,
No evidence for nuclear introgression despite complete mtDNA replacement in the Carpathian newt (Lissotriton montandoni).
2013,
Pubmed
