Signatures of positive selection in Toll-like receptor (TLR) genes in mammals

Abstract

BackgroundToll-like receptors (TLRs) are a major class of pattern recognition receptors (PRRs) expressed in the cell surface or membrane compartments of immune and non-immune cells. TLRs are encoded by a multigene family and represent the first line of defense against pathogens by detecting foreigner microbial molecular motifs, the pathogen-associated molecular patterns (PAMPs). TLRs are also important by triggering the adaptive immunity in vertebrates. They are characterized by the presence of leucine-rich repeats (LRRs) in the ectodomain, which are associated with the PAMPs recognition. The direct recognition of different pathogens by TLRs might result in different evolutionary adaptations important to understand the dynamics of the host-pathogen interplay. Ten mammal TLR genes, viral (TLR3, 7, 8, 9) and non-viral (TLR1-6, 10), were selected to identify signatures of positive selection that might have been imposed by interacting pathogens and to clarify if viral and non-viral TLRs might display different patterns of molecular evolution.ResultsBy using Maximum Likelihood approaches, evidence of positive selection was found in all the TLRs studied. The number of positively selected codons (PSC) ranged between 2-26 codons (0.25%-2.65%) with the non-viral TLR4 as the receptor with higher percentage of positively selected codons (2.65%), followed by the viral TLR8 (2.50%). The results indicated that viral and non-viral TLRs are similarly under positive selection. Almost all TLRs have at least one PSC located in the LRR ectodomain which underlies the importance of the pathogen recognition by this region.ConclusionsOur results are not in line with previous studies on primates and birds that identified more codons under positive selection in non-viral TLRs. This might be explained by the fact that both primates and birds are homogeneous groups probably being affected by only a restricted number of related viruses with equivalent motifs to be recognized. The analyses performed in this work encompassed a large number of species covering some of the most representative mammalian groups - Artiodactyla, Rodents, Carnivores, Lagomorphs and Primates - that are affected by different families of viruses. This might explain the role of adaptive evolution in shaping viral TLR genes.

Protein evolution of Toll-like receptors 4, 5 and 7 within Galloanserae birds

“…No positive selection signatures were detected in the intracellular TIR domain, which suggests that positive selection acts mainly on ligand-binding regions. This confirms the results of similar analyses undertaken on mammals [7,9,10,88,89] and amniotes [22]. Projection of positively selected and functionally important sites onto 3D protein models of GaGaTLR revealed changes at six positions (TLR4: 343; TLR5: 180, 209, 342, 379; TLR7: 26) that could directly influence receptor expression or function (Figures 2, 3 and 4, see Additional file 1: Tables S7 and S8 and Additional file 3: Section S4).…”

Maximum-likelihood approaches reveal signatures of positive selection in IL genes in mammals

“…For a more conservative approach, and as used previously, 43,44 only sites detected to be under positive selection in more than one ML method were considered. Alterations in coding regions of genes that lead to amino acids substitutions can induce changes in protein conformation.…”

Phylogeny of Host Response Proteins Activated in Silkworm Bombyx mori in Response to Infestation by Dipteran Endoparasitoid Revealed Functional Divergence and Temporal Molecular Adaptive Evolution

“…The phylogram showed that in B. mori, Toll had evolved at a later stage of evolution presumably due to slow but accumulated demand (77% varied amino acids and six replacements; Table 3) by pathogen invasion to activate immune responses which is a recent adaptation in holometabolous insects [56,80,81]. Thus the BmToll is under strong evolutionary pressure by infections in different higher organisms including human beings [56,82,83].…”