Diversification of the expanded teleost-specific toll-like receptor family in Atlantic cod, <it>Gadus morhua</it>

• Main Authors: Sundaram Arvind YM, Kiron Viswanath, Dopazo Joaquín, Fernandes Jorge MO
• Format: Article
• Language: English
• Published: BMC 2012-12-01
• Series: BMC Evolutionary Biology
• Subjects: Atlantic cod; Toll-like receptors; TLR; Innate immunity; Positive selection; Thermal stress; Neofunctionalisation
• Online Access: http://www.biomedcentral.com/1471-2148/12/256

<p>Abstract</p> <p>Background</p> <p>Toll-like receptors (Tlrs) are major molecular pattern recognition receptors of the innate immune system. Atlantic cod (<it>Gadus morhua</it>) 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.</p> <p>Results</p> <p>In this study, one <it>tlr21</it>, 12 <it>tlr22</it> and two <it>tlr23</it> genes representing the teleost-specific Tlr family have been cloned and characterised in cod. Phylogenetic analysis grouped all <it>tlr22</it> genes under a single clade, indicating that the multiple cod paralogues have arisen through lineage-specific duplications. All <it>tlr</it>s 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 <it>tlr</it>s were also differentially regulated following immune challenge by immersion with <it>Vibrio anguillarum</it>, 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 <it>tlr22d</it> transcript levels in spleen. Maximum likelihood analysis with different evolution models revealed that <it>tlr22</it> 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.</p> <p>Conclusion</p> <p>Positive selection pressure coupled with experimental evidence of differential expression strongly support the hypothesis that teleost-specific <it>tlr</it> paralogues in cod are undergoing neofunctionalisation and can recognise bacterial pathogen-associated molecular patterns to compensate for the lack of other cell surface Tlrs.</p>