MHC class I evolution; from Northern pike to salmonids

Abstract

Background: Salmonids are of major importance both as farmed and wild animals. With the changing environment comes changes in pathogenic pressures so understanding the immune system of all salmonid species is of essence. Major histocompatibility complex (MHC) genes are key players in the adaptive immune system signalling infection to responding T-cells populations. Classical MHC class I (MHCI) genes, defined by high polymorphism, broad expression patterns and peptide binding ability, have a key role in inducing immunity. In salmonids, the fourth whole genome duplication that occurred 94 million years ago has provided salmonids with duplicate MHCI regions, while Northern Pike, a basal sister clade to salmonids, represent a species which has not experienced this whole genome duplication.

Results: Comparing the gene organization and evolution of MHC class I gene sequences in Northern pike versus salmonids displays a complex picture of how many of these genes evolved. Regional salmonid Ia and Ib Z lineage gene duplicates are not orthologs to the Northern pike Z lineage sequences. Instead, salmonids have experienced unique gene duplications in both duplicate regions as well as in the Salmo and Oncorhynchus branch. Species-specific gene duplications are even more pronounced for some L lineage genes.

Conclusions: Although both Northern pike as well as salmonids have expanded their U and Z lineage genes, these gene duplications occurred separately in pike and in salmonids. However, the similarity between these duplications suggest the transposable machinery was present in a common ancestor. The salmonid MHCIa and MHCIb regions were formed during the 94 MYA since the split from pike and before the Oncorhynchus and Salmo branch separated. As seen in tetrapods, the non-classical U lineage genes are diversified duplicates of their classical counterpart. One MHCI lineage, the L lineage, experienced massive species-specific gene duplications after Oncorhynchus and Salmo split approximately 25 MYA. Based on what we currently know about L lineage genes, this large variation in number of L lineage genes also signals a large functional diversity in salmonids.

Keywords: Evolution; MHC class I; Northern pike; Phylogeny; Salmonids; Whole genome duplication.

Fig. 1

Phylogeny of Salmonidae and Northern pike. Phylogenetic relationship between included species. Dating of individual events are based on data from [48, 49]. Salmo and Oncorhynchus species are shown using a blue and red box respectively. The unique salmonid whole genome duplication event that occurred approximately 94 million years ago (MYA) [5] is shown using a red arrow

Fig. 2

Phylogeny of deduced U lineage alpha 1 domain amino acid sequences. Lineages are shown using roman numbers as defined by Grimholt et al. [8]. Strongly supported clades are shown using coloured boxes. The tree with the highest log likelihood (− 3618,84) is shown. The percentage of trees in which the associated taxa clustered together is shown next to the branches. A discrete Gamma distribution was used to model evolutionary rate differences among sites (5 categories (+ G, parameter = 1,5774)). The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. The analysis involved 59 amino acid sequences. There were a total of 85 positions in the final dataset. Atlantic salmon sequence references not present in Additional file 4 are as follows: UBA*0101 AAN75113, UBA*0201 AF504023, UBA*0301 AAN75116.1, UBA*0701 AAN75109, UBA*0801 AAN75115, UBA*0901 AAN75119, UBA*1001 AAN75118, UBA1101 AF504017.1, UBA*1401 AAN75110, UBA3301 DQ091795.1

Fig. 3

Phylogeny of deduced extracellular Z lineage amino acid sequences. The tree with the highest log likelihood (− 3771,17) is shown. The percentage of trees in which the associated taxa clustered together is shown next to the branches. A discrete Gamma distribution was used to model evolutionary rate differences among sites [5 categories (+ G, parameter = 0,3726)]. The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. The analysis involved 40 amino acid sequences. There were a total of 282 positions in the final dataset. The different (sub)clades are shown using coloured boxes

Fig. 4

Comparison of L lineage regions from salmonids and Northern pike. Genomic regions containing L lineage genes clustering in phylogenetic analyses and based on regional orthology. Genes represented by boxes are colour shaded as follows: red boxes are L lineage genes, green boxes are flanking genes found in most regions and grey boxes are other genes. Additional colour shading is used for regions from each species. Regional location is shown on the side of each region and species and chromosome when available is shown below. Details of unplaced scaffolds can be found in Additional file 3. Atlantic salmon and rainbow trout genes are on homeolog chromosomes (see Additional file 1), orthology to brown trout chromosomes is undefined and regions from the remaining species are all unplaced scaffolds (NW), thus proving no informative on orthology. Pseudogenes are shown using ψ while partial genes are shown using a pt name extension. Many genes have the extension _L for _like as they need further phylogenetic and functional studies to warrant a definite gene name.

Fig. 5

Phylogeny of deduced extracellular L lineage amino acid sequences. The tree with the highest log likelihood (− 6285,74) is shown. The percentage of trees in which the associated taxa clustered together is shown next to the branches. A discrete Gamma distribution was used to model evolutionary rate differences among sites [5 categories (+ G, parameter = 0,7617)]. The tree is drawn to scale, with branch lengths measured in the number of substitutions per site. There were a total of 269 positions in the final dataset. Strongly supported clusters are shown using colour shaded boxes