ArticleGenome biology and evolution2020
Evolutionary History of the Toll-Like Receptor Gene Family across Vertebrates.
Article in Genome biology and evolution, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 118 citations in OpenAlex.
- Genomic investigations of successful invasions: the picture emerging from recent studies.Biological reviews of the Cambridge Philosophical Society · 2025Pooled it
- Systematic review of structural and immunological features of mollusk toll-like receptors in aquaculture context.Frontiers in immunology · 2025Pooled it
- Evolutionary Response Patterns of the RodentEcology and evolution · 2026Article
- Divergent cis-regulatory haplotypes at Tlr2 are associated with immune responsiveness.Molecular biology and evolution · 2026Article
- Absence of Toll-like Receptor 21 (Biology · 2026Article
- Toll-like receptors in fish: evolution, structure, immune signaling, and translational prospects for adjuvant-based vaccine design in aquaculture.Frontiers in immunology · 2026Review
- Small RNA and Toll-like receptor interactions: origins and disease mechanisms.Trends in biochemical sciences · 2025Review
- LPS binding caspase activation and recruitment domains (CARDs) are bipartite lipid binding modules.Science advances · 2025Article
- Innate Immunity Toll-Like Triad TLR6-1-10 and Its Diversity in Distinct Horse Breeds.Veterinary medicine and science · 2025Article
- Tracing the paths of modular evolution by quantifying rearrangement events of protein domains.BMC ecology and evolution · 2025Article
- Genome-wide identification and characterisation of Toll-like receptors in Chinese spiny frog (Frontiers in genetics · 2025Article
- Role of endosomal toll-like receptors in immune sensing ofFrontiers in immunology · 2025Article
- LPS binding caspase activation and recruitment domains (CARDs) are bipartite lipid binding modules.bioRxiv : the preprint server for biology · 2024Article
- Viperin immunity evolved across the tree of life through serial innovations on a conserved scaffold.Nature ecology & evolution · 2024Article
- TLR7 in channel catfish (Ictalurus punctatus) is expressed in the endolysosome and is stimulated by synthetic ssRNA analogs, imiquimod, and resiquimod.Developmental and comparative immunology · 2024Article
- A new method for ecologists to estimate heterozygote excess and deficit for multi-locus gene families.Ecology and evolution · 2024Article
- Twelve toll-like receptor (TLR) genes in the family Equidae - comparative genomics, selection and evolution.Veterinary research communications · 2024Article
- Co-imaging of RelA and c-Rel reveals features of NF-κB signaling for ligand discrimination.Cell reports · 2024Article
- Extraction of Innate Immune Genes in Dairy Cattle and the Regulation of Their Expression in Early Embryos.Genes · 2024Review
- Immune receptors and aging brain.Bioscience reports · 2024Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adaptation to a wide range of pathogenic environments is a major aspect of the ecological adaptations of vertebrates during evolution. Toll-like receptors (TLRs) are ancient membrane-bound sensors in animals and are best known for their roles in detecting and defense against invading pathogenic microorganisms. To understand the evolutionary history of the vertebrate TLR gene family, we first traced the origin of single-cysteine cluster TLRs that share the same protein architecture with vertebrate TLRs in early-branching animals and then analyzed all members of the TLR family in over 200 species covering all major vertebrate clades. Our results indicate that although the emergence of single-cysteine cluster TLRs predates the separation of bilaterians and cnidarians, most vertebrate TLR members originated shortly after vertebrate emergence. Phylogenetic analyses divided 1,726 vertebrate TLRs into 8 subfamilies, and TLR3 may represent the most ancient subfamily that emerged before the branching of deuterostomes. Our analysis reveals that purifying selection predominated in the evolution of all vertebrate TLRs, with mean dN/dS (ω) values ranging from 0.082 for TLR21 in birds to 0.434 for TLR11 in mammals. However, we did observe patterns of positive selection acting on specific codons (527 of 60,294 codons across all vertebrate TLRs, 8.7‰), which are significantly concentrated in ligand-binding extracellular domains and suggest host-pathogen coevolutionary interactions. Additionally, we found stronger positive selection acting on nonviral compared with viral TLRs, indicating the more essential nonredundant function of viral TLRs in host immunity. Taken together, our findings provide comprehensive insight into the complex evolutionary processes of the vertebrate TLR gene family, involving gene duplication, pseudogenization, purification, and positive selection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.