@article {513, title = {Diversification of the expanded teleost-specific toll-like receptor family in Atlantic cod, Gadus morhua.}, journal = {BMC Evol Biol}, volume = {12}, year = {2012}, month = {2012 Dec 29}, pages = {256}, abstract = {

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{\textdegree}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.

}, keywords = {Amino Acid Sequence, Animals, Binding Sites, Evolution, Molecular, Fish Diseases, Fish Proteins, Gadus morhua, Gene Expression Profiling, Genetic Variation, Gills, Head Kidney, Host-Pathogen Interactions, Models, Molecular, Molecular Sequence Data, Multigene Family, Phylogeny, Protein Structure, Tertiary, Reverse Transcriptase Polymerase Chain Reaction, Selection, Genetic, Sequence Analysis, DNA, Sequence Homology, Amino Acid, Temperature, Toll-Like Receptors, Vibrio}, issn = {1471-2148}, doi = {10.1186/1471-2148-12-256}, author = {Sundaram, Arvind Y M and Kiron, Viswanath and Dopazo, Joaquin and Fernandes, Jorge M O} } @article {603, title = {DBAli tools: mining the protein structure space.}, journal = {Nucleic Acids Res}, volume = {35}, year = {2007}, month = {2007 Jul}, pages = {W393-7}, abstract = {

The DBAli tools use a comprehensive set of structural alignments in the DBAli database to leverage the structural information deposited in the Protein Data Bank (PDB). These tools include (i) the DBAlit program that allows users to input the 3D coordinates of a protein structure for comparison by MAMMOTH against all chains in the PDB; (ii) the AnnoLite and AnnoLyze programs that annotate a target structure based on its stored relationships to other structures; (iii) the ModClus program that clusters structures by sequence and structure similarities; (iv) the ModDom program that identifies domains as recurrent structural fragments and (v) an implementation of the COMPARER method in the SALIGN command in MODELLER that creates a multiple structure alignment for a set of related protein structures. Thus, the DBAli tools, which are freely accessible via the World Wide Web at http://salilab.org/DBAli/, allow users to mine the protein structure space by establishing relationships between protein structures and their functions.

}, keywords = {Algorithms, Amino Acid Sequence, Computational Biology, Data Interpretation, Statistical, Databases, Protein, Internet, Molecular Sequence Data, Protein Conformation, Proteins, Pseudomonas aeruginosa, Sequence Alignment, Sequence Analysis, Protein, Sequence Homology, Amino Acid, Software, Structure-Activity Relationship}, issn = {1362-4962}, doi = {10.1093/nar/gkm236}, author = {Marti-Renom, Marc A and Pieper, Ursula and Madhusudhan, M S and Rossi, Andrea and Eswar, Narayanan and Davis, Fred P and Al-Shahrour, F{\'a}tima and Dopazo, Joaquin and Sali, Andrej} }