O. Neill, L. Bryant, C. Doyle, and S. , Therapeutic Targeting of Toll-Like Receptors for Infectious and Inflammatory Diseases and Cancer, Pharmacological Reviews, vol.61, issue.2, pp.177-197, 2009.
DOI : 10.1124/pr.109.001073

S. Rakoff-nahoum and R. Medzhitov, Toll-like receptors and cancer, Nature Reviews Cancer, vol.5, issue.1, pp.57-63, 2009.
DOI : 10.1182/blood-2007-05-088682

G. Barton and J. Kagan, A cell biological view of Toll-like receptor function: regulation through compartmentalization, Nature Reviews Immunology, vol.321, issue.8, pp.535-542, 2009.
DOI : 10.1038/nri2587

S. Akira, S. Uematsu, and O. Takeuchi, Pathogen Recognition and Innate Immunity, Cell, vol.124, issue.4, pp.783-801, 2006.
DOI : 10.1016/j.cell.2006.02.015

O. Takeuchi and S. Akira, Pattern Recognition Receptors and Inflammation, Cell, vol.140, issue.6, pp.805-820, 2010.
DOI : 10.1016/j.cell.2010.01.022

J. Roach, G. Glusman, L. Rowen, A. Kaur, M. Purcell et al., The evolution of vertebrate Toll-like receptors, Proceedings of the National Academy of Sciences, vol.102, issue.27, pp.9577-9582, 2005.
DOI : 10.1073/pnas.0502272102

M. Carty and A. Bowie, Recent insights into the role of Toll-like receptors in viral infection, Clinical & Experimental Immunology, vol.24, issue.3, 2010.
DOI : 10.1111/j.1365-2249.2010.04196.x

A. Chaturvedi, How Location Governs Toll-Like Receptor Signaling, Traffic, vol.7, issue.6, pp.621-628, 2009.
DOI : 10.1111/j.1600-0854.2009.00899.x

G. Barton, Viral recognition by Toll-like receptors, Seminars in Immunology, vol.19, issue.1, pp.33-40, 2007.
DOI : 10.1016/j.smim.2007.01.003

J. Bell, G. Mullen, C. Leifer, A. Mazzoni, D. Davies et al., Leucine-rich repeats and pathogen recognition in Toll-like receptors, Trends in Immunology, vol.24, issue.10, pp.528-533, 2003.
DOI : 10.1016/S1471-4906(03)00242-4

B. Beutler, Z. Jiang, P. Georgel, K. Crozat, B. Croker et al., GENETIC ANALYSIS OF HOST RESISTANCE: Toll-Like Receptor Signaling and Immunity at Large, Annual Review of Immunology, vol.24, issue.1, pp.353-389, 2006.
DOI : 10.1146/annurev.immunol.24.021605.090552

R. Medzhitov, C. Janeway, and . Jr, Innate Immunity: The Virtues of a Nonclonal System of Recognition, Cell, vol.91, issue.3, pp.295-298, 1997.
DOI : 10.1016/S0092-8674(00)80412-2

R. Bhattacharjee and S. Akira, Toll-Like Receptor Signaling: Emerging Opportunities in Human Diseases and Medicine, Current Immunology Reviews, vol.1, issue.1, pp.81-90, 2005.
DOI : 10.2174/1573395052952897

J. Zhu and C. Mohan, Toll-Like Receptor Signaling Pathways???Therapeutic Opportunities, Mediators of Inflammation, vol.170, issue.6, p.781235, 2010.
DOI : 10.1002/art.24760

M. Jin, S. Kim, J. Heo, M. Lee, H. Kim et al., Crystal Structure of the TLR1-TLR2 Heterodimer Induced by Binding of a Tri-Acylated Lipopeptide, Cell, vol.130, issue.6, pp.1071-1082, 2007.
DOI : 10.1016/j.cell.2007.09.008

H. Kim, B. Park, J. Kim, S. Kim, J. Lee et al., Crystal Structure of the TLR4-MD-2 Complex with Bound Endotoxin Antagonist Eritoran, Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist Eritoran, pp.906-917, 2007.
DOI : 10.1016/j.cell.2007.08.002

T. Wei, J. Gong, F. Jamitzky, W. Heckl, R. Stark et al., Homology modeling of human Toll-like receptors TLR7, 8, and 9 ligand-binding domains, Protein Science, vol.90, issue.8, pp.1684-1691, 2009.
DOI : 10.1002/pro.186

I. Letunic, T. Doerks, and P. Bork, SMART 6: recent updates and new developments, Nucleic Acids Research, vol.37, issue.Database, pp.229-232, 2009.
DOI : 10.1093/nar/gkn808

URL : http://doi.org/10.1093/nar/gkn808

V. Offord, T. Coffey, and D. Werling, LRRfinder: A web application for the identification of leucine-rich repeats and an integrative Toll-like receptor database, Developmental & Comparative Immunology, vol.34, issue.10, pp.1035-1041, 2010.
DOI : 10.1016/j.dci.2010.05.004

J. Choe, M. Kelker, and I. Wilson, Crystal Structure of Human Toll-Like Receptor 3 (TLR3) Ectodomain, Science, vol.309, issue.5734, pp.581-585, 2005.
DOI : 10.1126/science.1115253

L. Liu, I. Botos, Y. Wang, J. Leonard, J. Shiloach et al., Structural Basis of Toll-Like Receptor 3 Signaling with Double-Stranded RNA, Science, vol.320, issue.5874, pp.379-381, 2008.
DOI : 10.1126/science.1155406

B. Park, D. Song, H. Kim, B. Choi, H. Lee et al., The structural basis of lipopolysaccharide recognition by the TLR4???MD-2 complex, Nature, vol.50, issue.7242, pp.1191-1195, 2009.
DOI : 10.1038/nature07830

Z. Chang, Important aspects of Toll-like receptors, ligands and their signaling pathways, Inflammation Research, vol.125, issue.Suppl 3, pp.791-808, 2010.
DOI : 10.1007/s00011-010-0208-2

S. Uematsu and S. Akira, Toll-Like Receptors (TLRs) and Their Ligands, Handb Exp Pharmacol, pp.1-20, 2008.
DOI : 10.1007/978-3-540-72167-3_1

Y. Guan, D. Ranoa, S. Jiang, S. Mutha, X. Li et al., Human TLRs 10 and 1 Share Common Mechanisms of Innate Immune Sensing but Not Signaling, The Journal of Immunology, vol.184, issue.9, pp.5094-5103, 2010.
DOI : 10.4049/jimmunol.0901888

U. Hasan, C. Chaffois, C. Gaillard, V. Saulnier, E. Merck et al., Human TLR10 Is a Functional Receptor, Expressed by B Cells and Plasmacytoid Dendritic Cells, Which Activates Gene Transcription through MyD88, The Journal of Immunology, vol.174, issue.5, pp.2942-2950, 2005.
DOI : 10.4049/jimmunol.174.5.2942

M. Yoneyama and T. Fujita, Recognition of viral nucleic acids in innate immunity, Reviews in Medical Virology, vol.316, issue.1, pp.4-22, 2010.
DOI : 10.1038/ni.1779

L. Alexopoulou, A. Holt, R. Medzhitov, and R. Flavell, Recognition of doublestranded RNA and activation of NF-kappaB by Toll-like receptor 3, Nature, vol.413, issue.6857, pp.732-738, 2001.
DOI : 10.1038/35099560

O. Takeuchi and S. Akira, Recognition of viruses by innate immunity, Immunological Reviews, vol.19, issue.1, pp.214-224, 2007.
DOI : 10.1016/j.immuni.2006.08.010

S. Janssens and R. Beyaert, Role of Toll-Like Receptors in Pathogen Recognition, Clinical Microbiology Reviews, vol.16, issue.4, pp.637-646, 2003.
DOI : 10.1128/CMR.16.4.637-646.2003

S. Mukherjee, N. Sarkar-roy, D. Wagener, and P. Majumder, Signatures of natural selection are not uniform across genes of innate immune system, but purifying selection is the dominant signature, Proceedings of the National Academy of Sciences, vol.106, issue.17, pp.7073-7078, 2009.
DOI : 10.1073/pnas.0811357106

L. Barreiro, M. Ben-ali, H. Quach, G. Laval, E. Patin et al., Evolutionary Dynamics of Human Toll-Like Receptors and Their Different Contributions to Host Defense, PLoS Genetics, vol.296, issue.7, p.1000562, 2009.
DOI : 10.1371/journal.pgen.1000562.s019

M. Ortiz, H. Kaessmann, K. Zhang, A. Bashirova, M. Carrington et al., The evolutionary history of the CD209 (DC-SIGN) family in humans and non-human primates, Genes and Immunity, vol.15, issue.6, pp.483-492, 2008.
DOI : 10.1038/gene.2008.40

T. Nakajima, H. Ohtani, Y. Satta, Y. Uno, H. Akari et al., Natural selection in the TLR-related genes in the course of primate evolution, Immunogenetics, vol.95, issue.W, pp.727-735, 2008.
DOI : 10.1007/s00251-008-0332-0

Y. Huang, N. Temperley, L. Ren, J. Smith, N. Li et al., Molecular evolution of the vertebrate TLR1 gene family - a complex history of gene duplication, gene conversion, positive selection and co-evolution, BMC Evolutionary Biology, vol.56, issue.9, p.149, 2011.
DOI : 10.1007/s00251-004-0734-6

M. Hamblin, E. Thompson, D. Rienzo, and A. , Complex Signatures of Natural Selection at the Duffy Blood Group Locus, The American Journal of Human Genetics, vol.70, issue.2, pp.369-383, 2002.
DOI : 10.1086/338628

E. Vallender and B. Lahn, Positive selection on the human genome, Human Molecular Genetics, vol.13, issue.suppl_2, pp.245-254, 2004.
DOI : 10.1093/hmg/ddh253

M. Alcaide and S. Edwards, Molecular Evolution of the Toll-Like Receptor Multigene Family in Birds, Molecular Biology and Evolution, vol.28, issue.5, 2011.
DOI : 10.1093/molbev/msq351

G. Wlasiuk and M. Nachman, Adaptation and Constraint at Toll-Like Receptors in Primates, Molecular Biology and Evolution, vol.27, issue.9, pp.2172-2186, 2010.
DOI : 10.1093/molbev/msq104

J. Rassa and S. Ross, Viruses and Toll-like receptors, Microbes and Infection, vol.5, issue.11, pp.961-968, 2003.
DOI : 10.1016/S1286-4579(03)00193-X

O. Jann, D. Werling, J. Chang, D. Haig, and E. Glass, Molecular evolution of bovine Toll-like receptor 2 suggests substitutions of functional relevance, BMC Evolutionary Biology, vol.8, issue.1, p.288, 2008.
DOI : 10.1186/1471-2148-8-288

T. Morozumi and H. Uenishi, Polymorphism distribution and structural conservation in RNA-sensing Toll-like receptors 3, 7, and 8 in pigs, Biochimica et Biophysica Acta (BBA) - General Subjects, vol.1790, issue.4, 2009.
DOI : 10.1016/j.bbagen.2009.01.002

R. Shimazu, S. Akashi, H. Ogata, Y. Nagai, K. Fukudome et al., MD-2, a Molecule that Confers Lipopolysaccharide Responsiveness on Toll-like Receptor 4, The Journal of Experimental Medicine, vol.161, issue.11, pp.1777-1782, 1999.
DOI : 10.1084/jem.180.4.1217

H. Kumar, T. Kawai, and S. Akira, Toll-like receptors and innate immunity, Biochemical and Biophysical Research Communications, vol.388, issue.4, pp.621-625, 2009.
DOI : 10.1016/j.bbrc.2009.08.062

D. Werling, O. Jann, V. Offord, E. Glass, and T. Coffey, Variation matters: TLR structure and species-specific pathogen recognition, Trends in Immunology, vol.30, issue.3, pp.124-130, 2009.
DOI : 10.1016/j.it.2008.12.001

R. Govindaraj, B. Manavalan, S. Basith, and S. Choi, Comparative Analysis of Species-Specific Ligand Recognition in Toll-Like Receptor 8 Signaling: A Hypothesis, PLoS ONE, vol.100, issue.9, p.25118, 2011.
DOI : 10.1371/journal.pone.0025118.s014

B. Manavalan, S. Basith, and S. Choi, Similar Structures but Different Roles ??? An Updated Perspective on TLR Structures, Frontiers in Physiology, vol.2, p.41, 2011.
DOI : 10.3389/fphys.2011.00041

X. Du, A. Poltorak, Y. Wei, and B. Beutler, Three novel mammalian toll-like receptors: gene structure, expression, and evolution, Eur Cytokine Netw, vol.11, pp.362-371, 2000.

T. Downing, A. Lloyd, O. Farrelly, C. Bradley, and D. , The Differential Evolutionary Dynamics of Avian Cytokine and TLR Gene Classes, The Journal of Immunology, vol.184, issue.12, pp.6993-7000, 2010.
DOI : 10.4049/jimmunol.0903092

J. Chen, T. Wang, T. Tzeng, C. Wang, and D. Wang, Evidence for positive selection in the TLR9 gene of teleosts, Fish & Shellfish Immunology, vol.24, issue.2, pp.234-242, 2008.
DOI : 10.1016/j.fsi.2007.11.005

A. Takaki, A. Yamazaki, T. Maekawa, H. Shibata, K. Hirayama et al., Positive selection of Toll-like receptor 2 polymorphisms in two closely related old world monkey species, rhesus and Japanese macaques, Immunogenetics, vol.95, issue.4, 2011.
DOI : 10.1007/s00251-011-0556-2

B. Tschirren, L. Raberg, and H. Westerdahl, Signatures of selection acting on the innate immunity gene Toll-like receptor 2 (TLR2) during the evolutionary history of rodents, Journal of Evolutionary Biology, vol.65, issue.6, pp.1232-1240, 2011.
DOI : 10.1111/j.1420-9101.2011.02254.x

P. Cormican, A. Lloyd, T. Downing, S. Connell, D. Bradley et al., The avian Toll-Like receptor pathway???Subtle differences amidst general conformity, Developmental & Comparative Immunology, vol.33, issue.9, pp.967-973, 2009.
DOI : 10.1016/j.dci.2009.04.001

B. Beutler and M. Rehli, Evolution of the TIR, Tolls and TLRs: Functional Inferences from Computational Biology, Curr Top Microbiol Immunol, vol.270, pp.1-21, 2002.
DOI : 10.1007/978-3-642-59430-4_1

B. Kobe and J. Deisenhofer, A structural basis of the interactions between leucine-rich repeats and protein ligands, Nature, vol.374, issue.6518, pp.183-186, 1995.
DOI : 10.1038/374183a0

S. Ewald, B. Lee, L. Lau, K. Wickliffe, G. Shi et al., The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor, Nature, vol.2, issue.7222, pp.658-662, 2008.
DOI : 10.1038/nature07405

E. Andersen-nissen, K. Smith, R. Bonneau, and R. Strong, A conserved surface on Toll-like receptor 5 recognizes bacterial flagellin, The Journal of Experimental Medicine, vol.2, issue.2, pp.393-403, 2007.
DOI : 10.1002/prot.10529

G. Wlasiuk, S. Khan, W. Switzer, and M. Nachman, A History of Recurrent Positive Selection at the Toll-Like Receptor 5 in Primates, Molecular Biology and Evolution, vol.26, issue.4, pp.937-949, 2009.
DOI : 10.1093/molbev/msp018

J. Jebanathirajah, S. Peri, and A. Pandey, Toll and interleukin-1 receptor (TIR) domain-containing proteins in plants: a genomic perspective, Trends in Plant Science, vol.7, issue.9, pp.388-391, 2002.
DOI : 10.1016/S1360-1385(02)02309-9

J. Turner, A bioinformatic approach to the identification of bacterial proteins interacting with Toll??????interleukin 1 receptor??????resistance (TIR) homology domains, FEMS Immunology & Medical Microbiology, vol.37, issue.1, pp.13-21, 2003.
DOI : 10.1016/S0928-8244(03)00095-6

Y. Xu, X. Tao, B. Shen, T. Horng, R. Medzhitov et al., Structural basis for signal transduction by the Toll/interleukin-1 receptor domains, Nature, vol.408, pp.111-115, 2000.

J. Slack, K. Schooley, T. Bonnert, J. Mitcham, E. Qwarnstrom et al., Identification of Two Major Sites in the Type I Interleukin-1 Receptor Cytoplasmic Region Responsible for Coupling to Pro-inflammatory Signaling Pathways, Journal of Biological Chemistry, vol.275, issue.7, pp.4670-4678, 2000.
DOI : 10.1074/jbc.275.7.4670

T. Hawn, A. Verbon, K. Lettinga, L. Zhao, S. Li et al., A Common Dominant TLR5 Stop Codon Polymorphism Abolishes Flagellin Signaling and Is Associated with Susceptibility to Legionnaires' Disease, The Journal of Experimental Medicine, vol.66, issue.10, pp.1563-1572, 2003.
DOI : 10.1016/S1074-7613(01)00201-1

M. Olson, When Less Is More: Gene Loss as an Engine of Evolutionary Change, The American Journal of Human Genetics, vol.64, issue.1, pp.18-23, 1999.
DOI : 10.1086/302219

M. Olson and A. Varki, Sequencing the chimpanzee genome: insights into human evolution and disease, Nature Reviews Genetics, vol.61, issue.1, pp.20-28, 2003.
DOI : 10.1038/nrg981

K. Choo, T. Tan, and S. Ranganathan, A comprehensive assessment of N-terminal signal peptides prediction methods, BMC Bioinformatics, vol.10, issue.Suppl 15, p.2, 2009.
DOI : 10.1186/1471-2105-10-S15-S2

I. Botos, L. Liu, Y. Wang, D. Segal, and D. Davies, The Toll-like receptor 3:dsRNA signaling complex, Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, vol.1789, issue.9-10, pp.667-674, 2009.
DOI : 10.1016/j.bbagrm.2009.06.005

M. Brinkmann, E. Spooner, K. Hoebe, B. Beutler, H. Ploegh et al., The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 is crucial for TLR signaling, The Journal of Cell Biology, vol.3, issue.2, pp.265-275, 2007.
DOI : 10.1146/annurev.immunol.21.120601.141126

T. Nishiya, E. Kajita, S. Miwa, and A. Defranco, TLR3 and TLR7 Are Targeted to the Same Intracellular Compartments by Distinct Regulatory Elements, Journal of Biological Chemistry, vol.280, issue.44, pp.37107-37117, 2005.
DOI : 10.1074/jbc.M504951200

E. Cargill and J. Womack, Detection of polymorphisms in bovine toll-like receptors 3, 7, 8, and 9, Genomics, vol.89, issue.6, pp.745-755, 2007.
DOI : 10.1016/j.ygeno.2007.02.008

I. Mikula, M. Bhide, and S. Pastorekova, Characterization of ovine TLR7 and TLR8 protein coding regions, detection of mutations and Maedi Visna virus infection, Veterinary Immunology and Immunopathology, vol.138, issue.1-2, pp.51-59, 2010.
DOI : 10.1016/j.vetimm.2010.06.015

P. Esteves, J. Abrantes, M. Carneiro, A. Muller, G. Thompson et al., Detection of positive selection in the major capsid protein VP60 of the rabbit haemorrhagic disease virus (RHDV), Virus Research, vol.137, issue.2, pp.253-256, 2008.
DOI : 10.1016/j.virusres.2008.07.025

J. Snoeck, J. Fellay, I. Bartha, D. Douek, and A. Telenti, Mapping of positive selection sites in the HIV-1 genome in the context of RNA and protein structural constraints, Retrovirology, vol.8, issue.1, p.87, 2011.
DOI : 10.1093/nar/gkl555

J. Drake, The Distribution of Rates of Spontaneous Mutation over Viruses, Prokaryotes, and Eukaryotes, Annals of the New York Academy of Sciences, vol.88, issue.1 MOLECULAR STR, pp.100-107, 1999.
DOI : 10.1007/BF00328720

S. Pond and S. Frost, Datamonkey: rapid detection of selective pressure on individual sites of codon alignments, Bioinformatics, vol.21, issue.10, pp.2531-2533, 2005.
DOI : 10.1093/bioinformatics/bti320

Z. Yang, PAML 4: Phylogenetic Analysis by Maximum Likelihood, Molecular Biology and Evolution, vol.24, issue.8, pp.1586-1591, 2007.
DOI : 10.1093/molbev/msm088

Z. Yang, R. Nielsen, N. Goldman, and A. Pedersen, Codon-substitution models for heterogeneous selection pressure at amino acid sites, Genetics, vol.155, pp.431-449, 2000.

K. Tamura, D. Peterson, N. Peterson, G. Stecher, M. Nei et al., MEGA5: Molecular Evolutionary Genetics Analysis Using Maximum Likelihood, Evolutionary Distance, and Maximum Parsimony Methods, Molecular Biology and Evolution, vol.28, issue.10, 2011.
DOI : 10.1093/molbev/msr121

Y. Wang, L. Geer, C. Chappey, J. Kans, and S. Bryant, Cn3D: sequence and structure views for Entrez, Trends in Biochemical Sciences, vol.25, issue.6, pp.300-302, 2000.
DOI : 10.1016/S0968-0004(00)01561-9

J. Kang, X. Nan, M. Jin, S. Youn, Y. Ryu et al., Recognition of Lipopeptide Patterns by Toll-like Receptor 2-Toll-like Receptor 6 Heterodimer, Immunity, vol.31, issue.6, pp.873-884, 2009.
DOI : 10.1016/j.immuni.2009.09.018