TY - JOUR T1 - Diversification of the expanded teleost-specific toll-like receptor family in Atlantic cod, Gadus morhua. JF - BMC Evol Biol Y1 - 2012 A1 - Sundaram, Arvind Y M A1 - Kiron, Viswanath A1 - Dopazo, Joaquin A1 - Fernandes, Jorge M O KW - Amino Acid Sequence KW - Animals KW - Binding Sites KW - Evolution, Molecular KW - Fish Diseases KW - Fish Proteins KW - Gadus morhua KW - Gene Expression Profiling KW - Genetic Variation KW - Gills KW - Head Kidney KW - Host-Pathogen Interactions KW - Models, Molecular KW - Molecular Sequence Data KW - Multigene Family KW - Phylogeny KW - Protein Structure, Tertiary KW - Reverse Transcriptase Polymerase Chain Reaction KW - Selection, Genetic KW - Sequence Analysis, DNA KW - Sequence Homology, Amino Acid KW - Temperature KW - Toll-Like Receptors KW - Vibrio AB -

BACKGROUND: Toll-like receptors (Tlrs) are major molecular pattern recognition receptors of the innate immune system. Atlantic cod (Gadus morhua) is the first vertebrate known to have lost most of the mammalian Tlr orthologues, particularly all bacterial recognising and other cell surface Tlrs. On the other hand, its genome encodes a unique repertoire of teleost-specific Tlrs. The aim of this study was to investigate if these duplicate Tlrs have been retained through adaptive evolution to compensate for the lack of other cell surface Tlrs in the cod genome.

RESULTS: In this study, one tlr21, 12 tlr22 and two tlr23 genes representing the teleost-specific Tlr family have been cloned and characterised in cod. Phylogenetic analysis grouped all tlr22 genes under a single clade, indicating that the multiple cod paralogues have arisen through lineage-specific duplications. All tlrs examined were transcribed in immune-related tissues as well as in stomach, gut and gonads of adult cod and were differentially expressed during early development. These tlrs were also differentially regulated following immune challenge by immersion with Vibrio anguillarum, indicating their role in the immune response. An increase in water temperature from 4 to 12°C was associated with a 5.5-fold down-regulation of tlr22d transcript levels in spleen. Maximum likelihood analysis with different evolution models revealed that tlr22 genes are under positive selection. A total of 24 codons were found to be positively selected, of which 19 are in the ligand binding region of ectodomain.

CONCLUSION: Positive selection pressure coupled with experimental evidence of differential expression strongly support the hypothesis that teleost-specific tlr paralogues in cod are undergoing neofunctionalisation and can recognise bacterial pathogen-associated molecular patterns to compensate for the lack of other cell surface Tlrs.

VL - 12 U1 - https://www.ncbi.nlm.nih.gov/pubmed/23273344?dopt=Abstract ER -