BACKGROUND: Toll-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. RESULTS: Physiochemical 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. CONCLUSIONS: Host-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.

• MeSH
• Anseriformes genetika   MeSH
• Galliformes genetika   MeSH
• lidé MeSH
• molekulární evoluce * MeSH
• myši MeSH
• počítačová simulace MeSH
• sekvenční analýza proteinů MeSH
• terciární struktura proteinů MeSH
• toll-like receptor 4 genetika   MeSH
• toll-like receptor 5 genetika   MeSH
• toll-like receptor 7 genetika   MeSH
• vazebná místa MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Toll-like receptors (TLRs) are a cornerstone of vertebrate innate immunity. In this study, we identified orthologues of TLR4, TLR5 and TLR7 (representing both bacterial- and viral-sensing TLRs) in the grey partridge (Perdix perdix), a European Galliform game bird species. The phylogeny of all three TLR genes follows the known phylogeny of Galloanserae birds, placing grey partridge TLRs (PePeTLRs) in close proximity to their turkey and pheasant orthologues. The predicted proteins encoded by the PePeTLR genes were 843, 862-863 and 1,047 amino acids long, respectively, and clearly showed all TLR structural features. To verify functionality in these genes we mapped their tissue-expression profiles, revealing generally high PePeTLR4 and PePeTLR5 expression in the thymus and absence of PePeTLR4 and PePeTLR7 expression in the brain. Using 454 next-generation sequencing, we then assessed genetic variation within these genes for a wild grey partridge population in the Czech Republic, EU. We identified 11 nucleotide substitutions in PePeTLR4, eight in PePeTLR5 and six in PePeTLR7, resulting in four, four and three amino acid replacements, respectively. Given their locations and chemical features, most of these non-synonymous substitutions probably have a minor functional impact. As the intraspecific genetic variation of the three TLR genes was low, we assume that either negative selection or a bottleneck may have reduced TLR population variability in this species.

• MeSH
• exprese genu MeSH
• fylogeneze MeSH
• Galliformes klasifikace   genetika   MeSH
• genetická variace * MeSH
• konformace proteinů MeSH
• molekulární evoluce MeSH
• molekulární modely MeSH
• orgánová specificita MeSH
• toll-like receptor 4 chemie   genetika   MeSH
• toll-like receptor 5 chemie   genetika   MeSH
• toll-like receptor 7 chemie   genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH