Origin and evolution of MHC class I and MIC genes in primates

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MHC system is considered to be originated in protochordata more than 300 million years ago, and has since been modified and refined in evolution up to the present system in vertebrates. In this process various evolutionary factors have been involved not only in MHC genic regions but also in other genomic regions. Therefore, it is desirable that evolutionary analysis be carried out in both the genic and non-genic regions in MHC genome sequences. We have made evolutionary analyses of a MHC Class I genomic region for man (M), chimpanzee (C) and Rhesus monkey (R) focusing particularly on the evolutionary origin of B and C genes and that of MICA and MICB genes. It is known that each pair is located respectively in a pair genome fragments that were originated by genome fragment duplication. To estimate the evolutionary origin of each pair of the genes, therefore, we were to estimate the duplication time of each pair of the genome fragments. It is noted that sine the MHC genes have been subject to strong positive selection in evolution, the genes have not evolved constantly over time making them unsuitable for the estimation. We thus paid attention to orthologous LINE fragments between the pair of the genome fragments that have coevolved with the MHC genes, but constantly over time because they have lost their functions before the duplication of the genome fragments. For calibration we adopted an estimate of the divergence time between man and chimpanzee as 5.4 million years (MY) ago. We then estimated the origin of MHC B and MHC C genes as far back as 22.3 MY ago, and that of MICA and MICE as far back as 14.1 MY ago. The validity of these estimates were confirmed by our new achievement that the divergence time of Rhesus monkey has been estimated as 27.0 MY ago.