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Open Access Highly Accessed Research article

Molecular evolution of the vertebrate TLR1 gene family - a complex history of gene duplication, gene conversion, positive selection and co-evolution

Yinhua Huang1, Nicholas D Temperley2, Liming Ren3, Jacqueline Smith1, Ning Li3 and David W Burt1*

Author affiliations

1 Division of Genetics and Genomics, The Roslin Institute and R(D)SVS, University of Edinburgh, Roslin, Midlothian EH25 9PS, UK

2 MRC Human Genetics Unit and the Division of Cancer Research, Institute of Genetics and Molecular Medicine, The University of Edinburgh, Crewe Road South, Edinburgh, EH4 2XR, UK

3 State Key Laboratory for Agrobiotechnology, China Agricultural University, Beijing 100094, People's Republic of China

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Citation and License

BMC Evolutionary Biology 2011, 11:149  doi:10.1186/1471-2148-11-149

Published: 28 May 2011

Abstract

Background

The Toll-like receptors represent a large superfamily of type I transmembrane glycoproteins, some common to a wide range of species and others are more restricted in their distribution. Most members of the Toll-like receptor superfamily have few paralogues; the exception is the TLR1 gene family with four closely related genes in mammals TLR1, TLR2, TLR6 and TLR10, and four in birds TLR1A, TLR1B, TLR2A and TLR2B. These genes were previously thought to have arisen by a series of independent gene duplications. To understand the evolutionary pattern of the TLR1 gene family in vertebrates further, we cloned the sequences of TLR1A, TLR1B, TLR2A and TLR2B in duck and turkey, constructed phylogenetic trees, predicted codons under positive selection and identified co-evolutionary amino acid pairs within the TLR1 gene family using sequences from 4 birds, 28 mammals, an amphibian and a fish.

Results

This detailed phylogenetic analysis not only clarifies the gene gains and losses within the TLR1 gene family of birds and mammals, but also defines orthologues between these vertebrates. In mammals, we predict amino acid sites under positive selection in TLR1, TLR2 and TLR6 but not TLR10. We detect co-evolution between amino acid residues in TLR2 and the other members of this gene family predicted to maintain their ability to form functional heterodimers. In birds, we predict positive selection in the TLR2A and TLR2B genes at functionally significant amino acid residues. We demonstrate that the TLR1 gene family has mostly been subject to purifying selection but has also responded to directional selection at a few sites, possibly in response to pathogen challenge.

Conclusions

Our phylogenetic and structural analyses of the vertebrate TLR1 family have clarified their evolutionary origins and predict amino acid residues likely to be important in the host's defense against invading pathogens.

Keywords:
Gene Duplication; Gene Conversion; Positive Selection; Co-evolution; TLR1 gene family