期刊论文详细信息
BMC Evolutionary Biology
Signatures of positive selection in Toll-like receptor (TLR) genes in mammals
Pedro J Esteves2  Joana Abrantes1  Helena Areal3 
[1] INSERM, U892, Universite de Nantes, 44007 Nantes, France;CITS, Centro de Investigacao em Tecnologias de Saude, CESPU, Gandra, Portugal;Departamento de Zoologia e Antropologia da Faculdade de Ciencias, Universidade do Porto, Porto, Portugal
关键词: non-viral TLRs;    viral TLRs;    positive selection;    adaptive evolution;    host-pathogen interaction;    PAMPs;    Toll-like receptors;   
Others  :  1141804
DOI  :  10.1186/1471-2148-11-368
 received in 2011-08-08, accepted in 2011-12-20,  发布年份 2011
PDF
【 摘 要 】

Background

Toll-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.

Results

By 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.

Conclusions

Our 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.

【 授权许可】

   
2011 Areal et al; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150327141945166.pdf 2096KB PDF download
Figure 4. 48KB Image download
Figure 3. 41KB Image download
Figure 2. 45KB Image download
Figure 1. 51KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】
  • [1]O'Neill LA, Bryant CE, Doyle SL: Therapeutic targeting of Toll-like receptors for infectious and inflammatory diseases and cancer. Pharmacol Rev 2009, 61:177-197.
  • [2]Rakoff-Nahoum S, Medzhitov R: Toll-like receptors and cancer. Nat Rev Cancer 2009, 9:57-63.
  • [3]Barton GM, Kagan JC: A cell biological view of Toll-like receptor function: regulation through compartmentalization. Nat Rev Immunol 2009, 9:535-542.
  • [4]Akira S, Uematsu S, Takeuchi O: Pathogen recognition and innate immunity. Cell 2006, 124:783-801.
  • [5]Takeuchi O, Akira S: Pattern recognition receptors and inflammation. Cell 2010, 140:805-820.
  • [6]Roach JC, Glusman G, Rowen L, Kaur A, Purcell MK, Smith KD, Hood LE, Aderem A: The evolution of vertebrate Toll-like receptors. Proc Natl Acad Sci USA 2005, 102:9577-9582.
  • [7]Takeda K, Kaisho T, Akira S: Toll-like receptors. Annu Rev Immunol 2003, 21:335-376.
  • [8]Carty M, Bowie AG: Recent insights into the role of Toll-like receptors in viral infection. Clin Exp Immunol 2010.
  • [9]Chaturvedi APS: How location governs toll-like receptor signaling. Traffic 2009, 10:621-628.
  • [10]Barton GM: Viral recognition by Toll-like receptors. Semin Immunol 2007, 19:33-40.
  • [11]Bell JK, Mullen GE, Leifer CA, Mazzoni A, Davies DR, Segal DM: Leucine-rich repeats and pathogen recognition in Toll-like receptors. Trends Immunol 2003, 24:528-533.
  • [12]Beutler B, Jiang Z, Georgel P, Crozat K, Croker B, Rutschmann S, Du X, Hoebe K: Genetic analysis of host resistance: Toll-like receptor signaling and immunity at large. Annu Rev Immunol 2006, 24:353-389.
  • [13]Medzhitov R, Janeway CA Jr: Innate immunity: the virtues of a nonclonal system of recognition. Cell 1997, 91:295-298.
  • [14]Bhattacharjee RN, Akira S: Toll-Like Receptor Signaling: Emerging Opportunities in Human Diseases and Medicine. Current Immunology Reviews 2005, 81-90.
  • [15]Zhu J, Mohan C: Toll-like receptor signaling pathways--therapeutic opportunities. Mediators Inflamm 2010, 2010:781235.
  • [16]Jin MS, Kim SE, Heo JY, Lee ME, Kim HM, Paik SG, Lee H, Lee JO: Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide. Cell 2007, 130:1071-1082.
  • [17]Kim HM, Park BS, Kim JI, Kim SE, Lee J, Oh SC, Enkhbayar P, Matsushima N, Lee H, Yoo OJ, Lee JO: Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran. Cell 2007, 130:906-917.
  • [18]Wei T, Gong J, Jamitzky F, Heckl WM, Stark RW, Rossle SC: Homology modeling of human Toll-like receptors TLR7, 8, and 9 ligand-binding domains. Protein Sci 2009, 18:1684-1691.
  • [19]Letunic I, Doerks T, Bork P: SMART 6: recent updates and new developments. Nucleic Acids Res 2009, 37:D229-232.
  • [20]Offord V, Coffey TJ, Werling D: LRRfinder: a web application for the identification of leucine-rich repeats and an integrative Toll-like receptor database. Dev Comp Immunol 2010, 34:1035-1041.
  • [21]Choe J, Kelker MS, Wilson IA: Crystal structure of human toll-like receptor 3 (TLR3) ectodomain. Science 2005, 309:581-585.
  • [22]Liu L, Botos I, Wang Y, Leonard JN, Shiloach J, Segal DM, Davies DR: Structural basis of toll-like receptor 3 signaling with double-stranded RNA. Science 2008, 320:379-381.
  • [23]Park BS, Song DH, Kim HM, Choi BS, Lee H, Lee JO: The structural basis of lipopolysaccharide recognition by the TLR4-MD-2 complex. Nature 2009, 458:1191-1195.
  • [24]Chang ZL: Important aspects of Toll-like receptors, ligands and their signaling pathways. Inflamm Res 2010, 59:791-808.
  • [25]Uematsu S, Akira S: Toll-Like receptors (TLRs) and their ligands. Handb Exp Pharmacol 2008, 1-20.
  • [26]Guan Y, Ranoa DR, Jiang S, Mutha SK, Li X, Baudry J, Tapping RI: Human TLRs 10 and 1 share common mechanisms of innate immune sensing but not signaling. J Immunol 2010, 184:5094-5103.
  • [27]Hasan U, Chaffois C, Gaillard C, Saulnier V, Merck E, Tancredi S, Guiet C, Briere F, Vlach J, Lebecque S, et al.: Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88. J Immunol 2005, 174:2942-2950.
  • [28]Yoneyama M, Fujita T: Recognition of viral nucleic acids in innate immunity. Rev Med Virol 2010, 20:4-22.
  • [29]Alexopoulou L, Holt AC, Medzhitov R, Flavell RA: Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3. Nature 2001, 413:732-738.
  • [30]Takeuchi O, Akira S: Recognition of viruses by innate immunity. Immunol Rev 2007, 220:214-224.
  • [31]Janssens S, Beyaert R: Role of Toll-like receptors in pathogen recognition. Clin Microbiol Rev 2003, 16:637-646.
  • [32]Mukherjee S, Sarkar-Roy N, Wagener DK, Majumder PP: Signatures of natural selection are not uniform across genes of innate immune system, but purifying selection is the dominant signature. Proc Natl Acad Sci USA 2009, 106:7073-7078.
  • [33]Barreiro LB, Ben-Ali M, Quach H, Laval G, Patin E, Pickrell JK, Bouchier C, Tichit M, Neyrolles O, Gicquel B, et al.: Evolutionary dynamics of human Toll-like receptors and their different contributions to host defense. PLoS Genet 2009, 5:e1000562.
  • [34]Ortiz M, Kaessmann H, Zhang K, Bashirova A, Carrington M, Quintana-Murci L, Telenti A: The evolutionary history of the CD209 (DC-SIGN) family in humans and non-human primates. Genes Immun 2008, 9:483-492.
  • [35]Nakajima T, Ohtani H, Satta Y, Uno Y, Akari H, Ishida T, Kimura A: Natural selection in the TLR-related genes in the course of primate evolution. Immunogenetics 2008, 60:727-735.
  • [36]Huang Y, Temperley ND, Ren L, Smith J, Li N, Burt DW: Molecular evolution of the vertebrate TLR1 gene family - a complex history of gene duplication, gene conversion, positive selection and co-evolution. BMC Evol Biol 2011, 11:149. BioMed Central Full Text
  • [37]Hamblin MT, Thompson EE, Di Rienzo A: Complex signatures of natural selection at the Duffy blood group locus. Am J Hum Genet 2002, 70:369-383.
  • [38]Vallender EJ, Lahn BT: Positive selection on the human genome. Hum Mol Genet 2004, 13(Spec No 2):R245-254.
  • [39]Alcaide M, Edwards SV: Molecular evolution of the Toll-like receptor multigene family in birds. Mol Biol Evol 2011.
  • [40]Wlasiuk G, Nachman MW: Adaptation and constraint at Toll-like receptors in primates. Mol Biol Evol 2010, 27:2172-2186.
  • [41]Rassa JC, Ross SR: Viruses and Toll-like receptors. Microbes Infect 2003, 5:961-968.
  • [42]Jann OC, Werling D, Chang JS, Haig D, Glass EJ: Molecular evolution of bovine Toll-like receptor 2 suggests substitutions of functional relevance. BMC Evol Biol 2008, 8:288. BioMed Central Full Text
  • [43]Morozumi T, Uenishi H: Polymorphism distribution and structural conservation in RNA-sensing Toll-like receptors 3, 7, and 8 in pigs. Biochim Biophys Acta 2009.
  • [44]Shimazu R, Akashi S, Ogata H, Nagai Y, Fukudome K, Miyake K, Kimoto M: MD-2, a molecule that confers lipopolysaccharide responsiveness on Toll-like receptor 4. J Exp Med 1999, 189:1777-1782.
  • [45]Kumar H, Kawai T, Akira S: Toll-like receptors and innate immunity. Biochem Biophys Res Commun 2009, 388:621-625.
  • [46]Werling D, Jann OC, Offord V, Glass EJ, Coffey TJ: Variation matters: TLR structure and species-specific pathogen recognition. Trends Immunol 2009, 30:124-130.
  • [47]Govindaraj RG, Manavalan B, Basith S, Choi S: Comparative analysis of species-specific ligand recognition in Toll-like receptor 8 signaling: a hypothesis. PLoS One 2011, 6:e25118.
  • [48]Manavalan B, Basith S, Choi S: Similar Structures but Different Roles - An Updated Perspective on TLR Structures. Front Physiol 2011, 2:41.
  • [49]Du X, Poltorak A, Wei Y, Beutler B: Three novel mammalian toll-like receptors: gene structure, expression, and evolution. Eur Cytokine Netw 2000, 11:362-371.
  • [50]Downing T, Lloyd AT, O'Farrelly C, Bradley DG: The differential evolutionary dynamics of avian cytokine and TLR gene classes. J Immunol 2010, 184:6993-7000.
  • [51]Chen JS, Wang TY, Tzeng TD, Wang CY, Wang D: Evidence for positive selection in the TLR9 gene of teleosts. Fish Shellfish Immunol 2008, 24:234-242.
  • [52]Janeway CA Jr, Medzhitov R: Innate immune recognition. Annu Rev Immunol 2002, 20:197-216.
  • [53]Takaki A, Yamazaki A, Maekawa T, Shibata H, Hirayama K, Kimura A, Hirai H, Yasunami M: Positive selection of Toll-like receptor 2 polymorphisms in two closely related old world monkey species, rhesus and Japanese macaques. Immunogenetics 2011.
  • [54]Tschirren B, Raberg L, Westerdahl H: Signatures of selection acting on the innate immunity gene Toll-like receptor 2 (TLR2) during the evolutionary history of rodents. J Evol Biol 2011, 24:1232-1240.
  • [55]Cormican P, Lloyd AT, Downing T, Connell SJ, Bradley D, O'Farrelly C: The avian Toll-Like receptor pathway--subtle differences amidst general conformity. Dev Comp Immunol 2009, 33:967-973.
  • [56]Beutler B, Rehli M: Evolution of the TIR, tolls and TLRs: functional inferences from computational biology. Curr Top Microbiol Immunol 2002, 270:1-21.
  • [57]Kobe B, Deisenhofer J: A structural basis of the interactions between leucine-rich repeats and protein ligands. Nature 1995, 374:183-186.
  • [58]Ewald SE, Lee BL, Lau L, Wickliffe KE, Shi GP, Chapman HA, Barton GM: The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor. Nature 2008, 456:658-662.
  • [59]Andersen-Nissen E, Smith KD, Bonneau R, Strong RK, Aderem A: A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin. J Exp Med 2007, 204:393-403.
  • [60]Wlasiuk G, Khan S, Switzer WM, Nachman MW: A history of recurrent positive selection at the toll-like receptor 5 in primates. Mol Biol Evol 2009, 26:937-949.
  • [61]Jebanathirajah JA, Peri S, Pandey A: Toll and interleukin-1 receptor (TIR) domain-containing proteins in plants: a genomic perspective. Trends Plant Sci 2002, 7:388-391.
  • [62]Turner JD: A bioinformatic approach to the identification of bacterial proteins interacting with Toll-interleukin 1 receptor-resistance (TIR) homology domains. FEMS Immunol Med Microbiol 2003, 37:13-21.
  • [63]Xu Y, Tao X, Shen B, Horng T, Medzhitov R, Manley JL, Tong L: Structural basis for signal transduction by the Toll/interleukin-1 receptor domains. Nature 2000, 408:111-115.
  • [64]Slack JL, Schooley K, Bonnert TP, Mitcham JL, Qwarnstrom EE, Sims JE, Dower SK: Identification of two major sites in the type I interleukin-1 receptor cytoplasmic region responsible for coupling to pro-inflammatory signaling pathways. J Biol Chem 2000, 275:4670-4678.
  • [65]Hawn TR, Verbon A, Lettinga KD, Zhao LP, Li SS, Laws RJ, Skerrett SJ, Beutler B, Schroeder L, Nachman A, et al.: A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires' disease. J Exp Med 2003, 198:1563-1572.
  • [66]Olson MV: When less is more: gene loss as an engine of evolutionary change. Am J Hum Genet 1999, 64:18-23.
  • [67]Olson MV, Varki A: Sequencing the chimpanzee genome: insights into human evolution and disease. Nat Rev Genet 2003, 4:20-28.
  • [68]Choo KH, Tan TW, Ranganathan S: A comprehensive assessment of N-terminal signal peptides prediction methods. BMC Bioinformatics 2009, 10(Suppl 15):S2. BioMed Central Full Text
  • [69]Botos I, Liu L, Wang Y, Segal DM, Davies DR: The toll-like receptor 3:dsRNA signaling complex. Biochim Biophys Acta 2009, 1789:667-674.
  • [70]Brinkmann MM, Spooner E, Hoebe K, Beutler B, Ploegh HL, Kim YM: The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 is crucial for TLR signaling. J Cell Biol 2007, 177:265-275.
  • [71]Nishiya T, Kajita E, Miwa S, Defranco AL: TLR3 and TLR7 are targeted to the same intracellular compartments by distinct regulatory elements. J Biol Chem 2005, 280:37107-37117.
  • [72]Cargill EJ, Womack JE: Detection of polymorphisms in bovine toll-like receptors 3, 7, 8, and 9. Genomics 2007, 89:745-755.
  • [73]Mikula I, Bhide M, Pastorekova S: Characterization of ovine TLR7 and TLR8 protein coding regions, detection of mutations and Maedi Visna virus infection. Vet Immunol Immunopathol 2010, 138:51-59.
  • [74]Esteves PJ, Abrantes J, Carneiro M, Muller A, Thompson G, van der Loo W: Detection of positive selection in the major capsid protein VP60 of the rabbit haemorrhagic disease virus (RHDV). Virus Res 2008, 137:253-256.
  • [75]Snoeck J, Fellay J, Bartha I, Douek DC, Telenti A: Mapping of positive selection sites in the HIV-1 genome in the context of RNA and protein structural constraints. Retrovirology 2011, 8:87. BioMed Central Full Text
  • [76]Drake JW: The distribution of rates of spontaneous mutation over viruses, prokaryotes, and eukaryotes. Ann N Y Acad Sci 1999, 870:100-107.
  • [77]Pond SL, Frost SD: Datamonkey: rapid detection of selective pressure on individual sites of codon alignments. Bioinformatics 2005, 21:2531-2533.
  • [78]Yang Z: PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol 2007, 24:1586-1591.
  • [79]Yang Z, Nielsen R, Goldman N, Pedersen AM: Codon-substitution models for heterogeneous selection pressure at amino acid sites. Genetics 2000, 155:431-449.
  • [80]Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S: MEGA5: Molecular Evolutionary Genetics Analysis using Maximum Likelihood, Evolutionary Distance, and Maximum Parsimony Methods. Mol Biol Evol 2011, in press.
  • [81]Wang Y, Geer LY, Chappey C, Kans JA, Bryant SH: Cn3D: sequence and structure views for Entrez. Trends Biochem Sci 2000, 25:300-302.
  • [82]Kang JY, Nan X, Jin MS, Youn SJ, Ryu YH, Mah S, Han SH, Lee H, Paik SG, Lee JO: Recognition of lipopeptide patterns by Toll-like receptor 2-Toll-like receptor 6 heterodimer. Immunity 2009, 31:873-884.
  文献评价指标  
  下载次数:16次 浏览次数:10次