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Open Access Research article

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

Helena Areal12, Joana Abrantes13 and Pedro J Esteves14*

Author affiliations

1 CIBIO-UP, Centro de Investigacao em Biodiversidade e Recursos Geneticos - Universidade do Porto, Campus Agrario de Vairao, Rua Padre Armando Quintas, nr.7, 4485-661 Vairao, Portugal

2 Departamento de Zoologia e Antropologia da Faculdade de Ciencias, Universidade do Porto, Porto, Portugal

3 INSERM, U892, Universite de Nantes, 44007 Nantes, France

4 CITS, Centro de Investigacao em Tecnologias de Saude, CESPU, Gandra, Portugal

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Citation and License

BMC Evolutionary Biology 2011, 11:368  doi:10.1186/1471-2148-11-368

Published: 20 December 2011

Abstract

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.

Keywords:
Toll-like receptors; PAMPs; host-pathogen interaction; adaptive evolution; positive selection; viral TLRs; non-viral TLRs