Fate of MHCII in salmonids following 4WGD

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Fate of MHCII in salmonids following 4WGD Unni Grimholt1   · Morten Lukacs1  Received: 31 August 2020 / Accepted: 11 November 2020 © The Author(s) 2020

Abstract Major histocompatibility complex (MHC) genes are key players in the adaptive immunity providing a defense against invading pathogens. Although the basic structures are similar when comparing mammalian and teleost MHC class II (MHCII) molecules, there are also clear-cut differences. Based on structural requirements, the teleosts non-classical MHCII molecules do not comply with a function similar to the human HLA-DM and HLA-DO, i.e., assisting in peptide loading and editing of classical MHCII molecules. We have previously studied the evolution of teleost class II genes identifying various lineages and tracing their phylogenetic occurrence back to ancient ray-finned fishes. We found no syntenic MHCII regions shared between cyprinids, salmonids, and neoteleosts, suggesting regional instabilities. Salmonids have experienced a unique whole genome duplication 94 million years ago, providing them with the opportunity to experiment with gene duplicates. Many salmonid genomes have recently become available, and here we set out to investigate how MHCII has evolved in salmonids using Northern pike as a diploid sister phyla, that split from the salmonid lineage prior to the fourth whole genome duplication (4WGD) event. We identified 120 MHCII genes in pike and salmonids, ranging from 11 to 20 genes per species analyzed where DB-group genes had the most expansions. Comparing the MHC of Northern pike with that of Atlantic salmon and other salmonids species provides a tale of gene loss, translocations, and genome rearrangements. Keywords  MHC class II · Salmonids · Northern pike · Evolution

Introduction In mammals, the core major histocompatibility complex (MHC) represents one gene dense genomic region of approximately 4 mega bases that contains MHC class I (MHCI) and MHC class II (MHCII) genes in addition to many other genes with or without immune function (Horton et al. 2004). The MHC genes themselves encode two different classes of molecules, MHC class I (MHCI) and MHC class II (MHCII), with many different genes within each class. Each MHC class is divided into either classical or non-classical genes where classical genes are highly polymorphic peptide-binders and non-classical genes deviate from this rule. Classical MHCI genes are expressed on most cells, encode molecules that bind and present self, and endogenously derived peptides to CD8 positive T cells, thus initiating a cellular This article is part of Topical Collection on Fish Immunogenetics * Unni Grimholt [email protected] 1



Norwegian Veterinary Institute, P.O. Box 8146 Dep, 0033 Oslo, Norway

immune response towards invading pathogens (Klein 1986). Classical MHCII genes encode molecules that in general bind and present exogenously derived peptides to CD4 positive T cells, thus initiating a humoral immune response towards the invading pathogens (Klein 1986). A classical MHCII gene is furth