Journal of Molecular Evolution

, Volume 65, Issue 2, pp 119–123 | Cite as

Evolutionary Analysis for Functional Divergence of the Toll-Like Receptor Gene Family and Altered Functional Constraints

  • Huaijun Zhou
  • Jianying Gu
  • Susan J. Lamont
  • Xun Gu


The Toll-like receptor (TLR) gene family consists of type 1 transmembrane receptors, which play essential roles in both innate immunity and adaptive immune response by ligand recognition and signal transduction. Using all available vertebrate TLR protein sequences, we inferred the phylogenetic tree and then characterized critical amino acid residues for functional divergence by detecting altered functional constraints after gene duplications. We found that the extracellular domain of TLR genes showed higher functional divergence than that of the cytoplasmic domain, particularly in the region between leucine-rich repeat (LRR) 10 and LRR 15 of TLR 4. Our finding supports the concept that sequence evolution in the extracellular domain may be responsible for the broad diversity of TLR ligand-binding affinity, providing a testable hypothesis for potential targets that could be verified by further experimentation.


Toll-like receptor Gene duplication Phylogenetic tree Functional divergence 


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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Huaijun Zhou
    • 1
    • 2
  • Jianying Gu
    • 1
  • Susan J. Lamont
    • 2
  • Xun Gu
    • 1
  1. 1.Department of Genetics, Development and Cell BiologyCenter for Bioinformatics and Biological Statistics, Iowa State UniversityAmesUSA
  2. 2.Department of Animal ScienceIowa State UniversityAmesUSA

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