Discovery of a Novel MHC Class I Lineage in Teleost Fish which Shows Unprecedented Levels of Ectodomain Deterioration while Possessing an Impressive Cytoplasmic Tail Motif

Abstract

A unique new nonclassical MHC class I lineage was found in Teleostei (teleosts, modern bony fish, e.g., zebrafish) and Holostei (a group of primitive bony fish, e.g., spotted gar), which was designated “H” (from “hexa”) for being the sixth lineage discovered in teleosts. A high level of divergence of the teleost sequences explains why the lineage was not recognized previously. The spotted gar H molecule possesses the three MHC class I consensus extracellular domains α1, α2, and α3. However, throughout teleost H molecules, the α3 domain was lost and the α1 domains showed features of deterioration. In fishes of the two closely related teleost orders Characiformes (e.g., Mexican tetra) and Siluriformes (e.g., channel catfish), the H ectodomain deterioration proceeded furthest, with H molecules of some fishes apparently having lost the entire α1 or α2 domain plus additional stretches within the remaining other (α1 or α2) domain. Despite these dramatic ectodomain changes, teleost H sequences possess rather large, unique, well-conserved tyrosine-containing cytoplasmic tail motifs, which suggests an important role in intracellular signaling. To our knowledge, this is the first description of a group of MHC class I molecules in which, judging from the sequence conservation pattern, the cytoplasmic tail is expected to have a more important conserved function than the ectodomain.

An Illumina approach to MHC typing of Atlantic salmon

“…In salmonids, there are six characterised MHC class I lineages defined based on sequence identity denoted U, Z, S, L, P and H lineages (Dijkstra et al 2007;Grimholt et al 2015;Grimholt et al 2019;Shum et al 1999;Stet et al 1998). Of these six lineages, only the U and Z lineages are peptide binders where the single classical locus UBA identified in rainbow trout and Atlantic salmon belongs to the U lineage (Grimholt et al 2015).…”

MHC class I evolution; from Northern pike to salmonids

“…We recently found a sixth MHC class I lineage in teleosts which we denoted the H lineage [13]. retained a function in some species.…”

“…Genome searches were performed using previously identi ed Atlantic salmon MHC gene sequences [5,13,36] and tblastn against selected salmonid genomes. Genomic regions identi ed through these searches were screened for annotated genes and sometimes regional genes were identi ed using additional blast searches.…”

“…In addition to the teleost speci c Z lineage mentioned above, we have de ned ve other teleost MHCI lineages denoted U, L, S, P and H [5,13,14]. The U lineage is composed of both classical as well as nonclassical peptide-binders.…”

“…Sequences from this H lineage show unprecedented deterioration of its extracellular domains, where teleosts have lost the alpha 3 domain as compared to their spotted gar orthologue. Also the alpha 1 and alpha 2 domains of teleost H lineage molecules is shorter in some species while the cytoplasmic tail has been conserved across divergent species [13]. The S lineage is only found in teleosts.…”