Evolution of HLA-F and its orthologues in primate species: a complex tale of conservation, diversification and inactivat
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ORIGINAL ARTICLE
Evolution of HLA‑F and its orthologues in primate species: a complex tale of conservation, diversification and inactivation N. Otting1,2 · N. G. de Groot1,2 · R. E. Bontrop1,2,3 Received: 27 August 2020 / Accepted: 3 November 2020 © The Author(s) 2020
Abstract HLA-F represents one of the nonclassical MHC class I molecules in humans. Its main characteristics involve low levels of polymorphism in combination with a restricted tissue distribution. This signals that the gene product executes a specialised function, which, however, is still poorly understood. Relatively little is known about the evolutionary equivalents of this gene in nonhuman primates, especially with regard to population data. Here we report a comparative genetic analysis of the orthologous genes of HLA-F in various great ape, Old World monkey (OWM), and New World monkey (NWM) species. HLA-F-related transcripts were found in all subjects studied. Low levels of polymorphism were encountered, although the length of the predicted gene products may vary. In most species, one or two transcripts were discovered, indicating the presence of only one active F-like gene per chromosome. An exception was provided by a New World monkey species, namely, the common marmoset. In this species, the gene has been subject to duplication, giving rise to up to six F-like transcripts per animal. In humans, great apes, and OWM, and probably the majority of the NWM species, the evolutionary equivalents of the HLA-F gene experienced purifying selection. In the marmoset, however, the gene was initially duplicated, but the expansion was subjected afterwards to various mechanisms of genetic inactivation, as evidenced by the presence of pseudogenes and an array of genetic artefacts in a section of the transcripts. Keywords HLA-F · MHC · Comparative genetics · Nonhuman primates
Introduction The classical HLA-A, -B, and -C molecules are highly polymorphic and are usually expressed on the cell surface of nucleated cells. They play an important role in the initiation and regulation of adaptive immune responses, by presenting peptides derived from intracellular pathogens to receptors on various types of T cells. Some of the polymorphic epitopes, born on classical MHC class I molecules, are recognised by ligands on natural killer cells (Parham, Guethlein 2018). * R. E. Bontrop [email protected]; [email protected] 1
Department of Comparative Genetics and Refinement, Biomedical Primate Research Centre, Rijswijk, The Netherlands
2
IPD-MHC Database Nonhuman Primate Nomenclature Committee, Rijswijk, The Netherlands
3
Department of Biology, Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, The Netherlands
The non-classical MHC class I molecules in humans are designated HLA-E, -F, and -G and are characterised by low levels of polymorphism. These gene products display a restricted tissue distribution, and generally, but not exclusively, interact with receptors of the innate immune system; for example, HLA-E is a monitor for the manipulation
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