High diversity of MIC genes in non-human primates
The human MHC class I (MHC-I) chain-related genes A and B (MICA and MICB) encode stress-induced glycoproteins, ligands for the activating receptor NKG2D. They display an unusually high degree of polymorphism, next only to that of classical MHC-I. The functional relevance and selective pressure behind this peculiar polymorphism, which is quite distinct from that of classical MHC-I, remain largely unknown. This study increases the repertoire of allelic sequences determined for the MIC genes of non-human primates. Sequencing (mainly exons 2, 3, 4, 5) MIC genes of 72 Macaca fascicularis (Mafa), 63 Pan troglodytes (Patr), and 18 Gorilla gorilla (Gogo) individuals led to the identification of 35, 14, and 3 new alleles, respectively. Additionally, we confirm the existence of three independent MIC genes in M. fascicularis, i.e., Mafa-MICA, Mafa-MICB, and Mafa-MICB/A, the latter being a hybrid of Mafa-MICB and Mafa-MICA. By multiple sequence alignment and phylogenetic analysis, we further demonstrate that the present day MIC genes most likely derive from a single human MICB-like ancestral gene.
KeywordsMHC class I chain-related genes Gorilla gorilla Pan troglodytes Macaca fascicularis Allelic diversity
We wish to thank Dr. Alejandro P. Rooney for the primate samples. This work is published under the framework of the LABEX TRANSPLANEX [ANR-11-LABX-0070_TRANSPLANTEX] which benefits from the funding of the French government, funds managed by the French National Research Agency (ANR) as part of the “Investments for the future” program. Additional support was provided by Genomax, the Strasbourg School of Medicine Next Generation Sequencing center, the French Ministry of Research, and the Institut Universitaire de France (IUF).
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