Insights into the evolution of extracellular leucine-rich repeats in metazoans with special reference to Toll-like receptor 4
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The importance of the widely spread leucine-rich repeat (LRR) motif was studied considering TLRs, the LRR-containing protein involved in animal immune response. The protein connects intracellular signalling with a chain of molecular interactions through the presence of LRRs in the ectodomain and TIR in the endodomain. Domain analyses with human TLR1-9 reported ectodomain with tandem repeats, transmembrane domain and TIR domain. The repeat number varied across members of TLR and remained characteristic to a particular member. Analysis of gene structure revealed absence of codon interruption with TLR3 and TLR4 as exceptions. Extensive study with TLR4 from metazoans confirmed the presence of 23 LRRs in tandem. Distinct clade formation using coding and amino acid sequence of individual repeats illustrated independent evolution. Although ectodomain and endodomain exhibited differential selection pressure, within the ectodomain, however, the individual repeats displayed positive, negative and neutral selection pressure depending on their structural and functional significance.
KeywordsCodon interruption domain architecture evolution gene structure intron phase leucine-rich repeat phylogenetics selection pressure tandem arrays Toll-like receptors
The authors gratefully acknowledge the facilities provided by the Centre for High-Performance Computing for Modern Biology (CHPC) in the University of Calcutta. The authors express their sincere gratitude to Dr Aditi Maulik, postdoctoral (Wellcome Trust) fellow at the Indian Institute of Science, and Ms Sucharita Das, senior research fellow at the University of Calcutta, who provided insight and expertise that greatly assisted this research work.
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