Evolutionary and functional insight into the teleost immune system — lessons learned from Atlantic cod and other teleosts

Abstract

Teleosts comprise a very diverse group of species where genome sequencing the last decade has revealed great variability regarding their genetic basis for immunity. With emphasis on the innate immune system, this thesis addresses evolutionary and functional aspects of teleost immunity using high-throughput sequencing and bioinformatics analysis tools. The losses and expansions of Toll-like receptors (TLR) and loss of Major Histocompatibility Complex class II (MHCII) were originally discovered in Atlantic cod. TLRs are a gene family of pattern recognition receptors central to the functionality of innate immunity. The first paper in this thesis describes the in-depth characterization of Atlantic cod TLRs. The TLR repertoire, extreme compared to other teleosts and vertebrates, indicated a correlation with MHCII loss. In addition there were signs of diversifying selection within the TLR gene expansions suggesting sub- and neofunctionalization of the duplicated genes. Recently, through the use of new genome resources from 66 teleost species and corresponding species phylogeny, the loss of MHCII from the entire Gadiformes order was established. Using these genomes and phylogeny, we established the correlation between MHCII loss and TLR expansion within the order of Gadiformes (cod-like fish species). Moreover, we established correlations between the TLR expansion, species maximum depth and species latitudinal distribution — likely proxies for environmental abiotic factors such as temperature. We also investigated another long sought after gene in Atlantic cod — the Myxovirus resistance gene (Mx) — a viral infection marker with unknown function and considered a part of the innate immune system. Adding the Mx related findings to the teleost phylogeny showed that the changes to the teleost immune system are of a successive nature. The timing of the phylogeny demonstrated that well-described large alterations in past environment such as oceanic oxygen levels, temperature and layout of tectonic plates overlapped with the changes to the teleost immune system — illustrating the combined effect of host-intrinsic, biotic and abiotic factors on the evolution of the teleost immune system.