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

Monica H Solbakken,Marit Seppola,Sissel Jentoft,Ole K Tørresen,Kjetill S Jakobsen,Alexander J Nederbragt,Tone F Gregers

doi:10.1038/srep25211

Monica H Solbakken, Marit Seppola + Show 5 more

Open Access

https://doi.org/10.1038/srep25211

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Abstract

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.

Highlights

Functional understanding of teleost immunity and its diversity is still in its infancy
We find that TLR7, TLR8, TLR9, TLR22 and TLR25 are expanded in Atlantic cod and that the gene copies display both tandem and non-tandem organization in numerous contigs (Fig. 2)
Our Toll-like receptors (TLR) phylogeny indicates that Atlantic cod is the only known species lacking TLR1/6 and TLR2 which is confirmed by gene synteny analysis (Figs 1 and 7)

Summary

Introduction

Functional understanding of teleost immunity and its diversity is still in its infancy Homologs of both mammalian innate and adaptive immune genes have been detected in teleost genomes, teleosts display greater genetic diversity as well as some functional discrepancies - for examples see references[1,2,3]. By taking advantage of a new and substantially improved genome assembly combined with large scale genomic analyses we here perform a deep characterization of the major innate immune gene families in Atlantic cod, with emphasis on TLRs. Our phylogenetic analysis shows that the gene losses and expansions in Atlantic cod are extreme compared to other vertebrate lineages, including other teleosts. A comprehensive vertebrate TLR phylogeny demonstrates that there is a shift in TLR repertoires following the transition from aquatic to terrestrial life styles mirroring different selective pressures in the two environments

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