Major histocompatibility complex (MHC) fragment numbers alone - in Atlantic cod and in general - do not represent functional variability.

Johannes M Dijkstra,Unni Grimholt

doi:10.12688/f1000research.15386.1

Abstract

This correspondence concerns a publication by Malmstrøm et al. in Nature Genetics in October 2016. Malmstrøm et al. made an important contribution to fish phylogeny research by using low-coverage genome sequencing for comparison of 66 teleost (modern bony) fish species, with 64 of those 66 belonging to the species-rich clade Neoteleostei, and with 27 of those 64 belonging to the order Gadiformes. For these 66 species, Malmstrøm et al. estimated numbers of genes belonging to the major histocompatibility complex (MHC) class I lineages U and Z and concluded that in teleost fish these combined numbers are positively associated with, and a driving factor of, the rates of establishment of new fish species (speciation rates). They also claimed that functional genes for the MHC class II system molecules MHC IIA, MHC IIB, CD4 and CD74 were lost in early Gadiformes. Our main criticisms are (1) that the authors did not provide sufficient evidence for presence or absence of intact functional MHC class I or MHC class II system genes, (2) that they did not discuss that an MHC subpopulation gene number alone is a very incomplete measure of MHC variance, and (3) that the MHC system is more likely to reduce speciation rates than to enhance them. We conclude that their new model of MHC class I evolution, reflected in their title "Evolution of the immune system influences speciation rates in teleost fish", is unsubstantiated. In addition, we explain that their "pinpointing" of the functional loss of the MHC class II system and all the important MHC class II system genes to the onset of Gadiformes is preliminary, because they did not sufficiently investigate the species at the clade border.

Highlights

This correspondence concerns a publication by Malmstrøm et al in Nature Genetics in October 2016
Not all teleost U and Z molecules are expected to present peptides[4,5], for example this is not expected for the majority of U lineage molecules in the neoteleost fish medaka[6] and the non-neoteleost fish rainbow trout[7]; how this is in the majority of the species investigated by Malmstrøm et al.[1] remains to be determined
It should be realized that major histocompatibility complex (MHC) class II and nonpeptide-binding MHC class I molecules can contribute to T cell depletione.g.8. While from their referencing it follows that Malmstrøm et al.[1] were aware of an MHC class II impact on T cell depletion, the authors did not look at MHC class II when investigating their optimum MHC number model

Summary

Introduction

This correspondence concerns a publication by Malmstrøm et al in Nature Genetics in October 2016. The correspondence by Dijkstra & Grimholt[1] provides critical concerns about a publication by Malmstrøm et al in Nature Genetics in October 20162, concluding that their new model of MHC class I evolution, reflected in their title “Evolution of the immune system influences speciation rates in teleost fish”, is unsubstantiated.

Results

Conclusion