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Genome sequencing of the teleost Atlantic cod demonstrated loss of the Major Histocompatibility Complex (MHC) class II, an extreme gene expansion of MHC class I and gene expansions and losses in the innate pattern recognition receptor (PRR) family of Toll-like receptors (TLR). In a comparative genomic setting, using an improved version of the genome, we characterize  PRRs  in Atlantic cod with emphasis on  TLRs  demonstrating the loss of  TLR1/6 ,  TLR2  and  TLR5  and expansion of  TLR7 ,  TLR8 ,  TLR9 ,  TLR22  and  TLR25 . We find that Atlantic cod  TLR  expansions are strongly influenced by diversifying selection likely to increase the detectable ligand repertoire through neo- and subfunctionalization. Using RNAseq we find that Atlantic cod  TLRs  display likely tissue or developmental stage-specific expression patterns. In a broader perspective, a comprehensive vertebrate  TLR  phylogeny reveals that the Atlantic cod  TLR  repertoire is extreme with regards to losses and expansions compared to other teleosts. In addition we identify a substantial shift in  TLR  repertoires following the evolutionary transition from an aquatic vertebrate (fish) to a terrestrial (tetrapod) life style. Collectively, our findings provide new insight into the function and evolution of  TLRs  in Atlantic cod as well as the evolutionary history of vertebrate innate immunity.

Evolutionary redesign of the Atlantic cod (Gadus morhua L.) Toll-like receptor repertoire by gene losses and expansions