Possible polyphyletic origin of major histocompatibility complex class I chain-related gene A (MICA) alleles

Phylogenetic relationships among 23 nonhuman primate (NHP) major histocompatibility complex class I chain-related gene (MIC) sequences, 54 confirmed human MICA alleles, and 16 human MICE alleles were constructed with methods of sequence analysis. Topology of the phylogenetic tree showed separation between NHP MICs and human MICs. For human MICs, the topology indicated monophyly for the MICB alleles, while MICA alleles were separated into two lineages, LI and LII. Of these, LI MICA alleles shared a common ancestry with gorilla (Ggo) MIC. One conservative amino acid difference and two nonconservative amino acid differences in the alpha3 domain were found between the MICA lineages. The nonconservative amino acid differences might imply structural and functional differences. Transmembrane (TM) trinucleotide-repeat variants were found to be specific to the MICA lineages such as A4, A9, and A10 to LI and A5 to LII. Variants such as A5.1 and A6 were commonly found in both MICA lineages. Based on these analyses, we postulate a polyphyletic origin for MICA alleles and their division into two lineages, LI and LII. As such, there would be 30 alleles in LI and 24 alleles in LII, thereby reducing the current level of polymorphism that exists, based on a presumed monophyletic origin. The lower degree of polymorphism in MICA would then be in line with the rest of the human major histocompatibility complex nonclassical class I genes.