Purifying selection shaping the evolution of the Toll-like receptor 2 TIR domain in brown hares (Lepus europaeus) from Europe and the Middle East

Stefanović, Milomir; Djan, Mihajla; Veličković, Nevena; Demirbaş, Yasin; Paule, Ladislav; Gedeon, Csongor I.; Posautz, Annika; Beiglböck, Christoph; Kübber‐Heiss, Anna; Suchentrunk, Franz

doi:10.1007/s11033-020-05382-x

Cited by 2 publications

(1 citation statement)

References 65 publications

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“…Upon recognition of specific ligands by TLRs, the TIR domain initiates the downstream signal transduction, interacting with host adaptor proteins ( 59 ). It is known that the TIR domains of different TLRs are highly conserved across animals and plants, being under strong negative selection ( 60 ). Our results are in line with this expectation since 85 out of 144 amino acids that compose the TIR domain are under negative selection.…”

Section: Discussionmentioning

confidence: 99%

Uncovering a 500 million year old history and evidence of pseudogenization for TLR15

et al. 2022

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IntroductionToll like receptors (TLRs) are at the front line of pathogen recognition and host immune response. Many TLR genes have been described to date with some being found across metazoans while others are restricted to specific lineages. A cryptic member of the TLR gene family, TLR15, has a unique phylogenetic distribution. Initially described in extant species of birds and reptiles, an ortholog has been reported for cartilaginous fish. MethodsHere, we significantly expanded the evolutionary analysis of TLR15 gene evolution, taking advantage of large genomic and transcriptomic resources available from different lineages of vertebrates. Additionally, we objectively search for TLR15 in lobe-finned and ray-finned fish, as well as in cartilaginous fish and jawless vertebrates.Results and discussionWe confirm the presence of TLR15 in early branching jawed vertebrates – the cartilaginous fish, as well as in basal Sarcopterygii – in lungfish. However, within cartilaginous fish, the gene is present in Holocephalans (all three families) but not in Elasmobranchs (its sister-lineage). Holocephalans have long TLR15 protein sequences that disrupt the typical TLR structure, and some species display a pseudogene sequence due to the presence of frameshift mutations and early stop codons. Additionally, TLR15 has low expression levels in holocephalans when compared with other TLR genes. In turn, lungfish also have long TLR15 protein sequences but the protein structure is not compromised. Finally, TLR15 presents several sites under negative selection. Overall, these results suggest that TLR15 is an ancient TLR gene and is experiencing ongoing pseudogenization in early-branching vertebrates.

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Section: Discussionmentioning

confidence: 99%

Uncovering a 500 million year old history and evidence of pseudogenization for TLR15

et al. 2022

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Beyond neutral loci: Examining immune gene variation in tigers(Panthera tigris)

Aditi,

Ramakrishnan

2024

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Isolated and inbred populations are at a higher risk to extinction due to the loss of genetic diversity. Carnivores are particularly susceptible to isolation due to their ecological requirements. Studies generally assess genetic vulnerability using neutral loci, but these may not accurately reflect a population’s adaptive potential. In contrast, diversity at loci putatively involved in fitness and hence survival, such as immune genes, could be a better proxy for future survival. Research on immune genes has traditionally focused on the MHC loci. We extend this investigation to five families of non-MHC immune genes - Tumor Necrosis Factor, Interleukin, Toll-like Receptor, Leukocyte Immunoglobulin Receptors, and Chemokine - involved in adaptive and innate immunity in tigers which exemplifies an endangered carnivore. We compare immune gene diversity to neutral diversity across the genome using whole genome resequencing data from 107 tigers, representing all extant subspecies and populations of different demographic histories.Our analysis reveals that immune receptor genes (mean nucleotide diversity: 0.0019) show high nucleotide diversity compared to neutral loci (0.0008) and immune signalling genes (0.0004) indicating past positive selection. Heterozygosity at the three classes of loci suggest that most immune genes are evolving neutrally. We confirm that small, isolated populations have lower nucleotide diversity and heterozygosity at both neutral and immune loci compared to large and connected populations. Additionally, genetic differentiation and deleterious mutation load correspond to known signatures from inbreeding and recent bottlenecks. Despite low neutral and immunogenetic diversity in small populations, some loci retain polymorphisms, irrespective of adaptive or innate immune functions. We conclude that drift is the predominant evolutionary force in bottlenecked populations even at adaptive loci.

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Purifying selection shaping the evolution of the Toll-like receptor 2 TIR domain in brown hares (Lepus europaeus) from Europe and the Middle East

Cited by 2 publications

References 65 publications

Uncovering a 500 million year old history and evidence of pseudogenization for TLR15

Uncovering a 500 million year old history and evidence of pseudogenization for TLR15

Beyond neutral loci: Examining immune gene variation in tigers(Panthera tigris)

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