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.
Cold-active enzymes have recently gained popularity because of their high activity at lower temperatures than their mesophilic and thermophilic counterparts, enabling them to withstand harsh reaction conditions and enhance industrial processes. Cold-active lipases are enzymes produced by psychrophiles that live and thrive in extremely cold conditions. Cold-active lipase applications are now growing in the detergency, synthesis of fine chemicals, food processing, bioremediation, and pharmaceutical industries. The cold adaptation mechanisms exhibited by these enzymes are yet to be fully understood. Using phylogenetic analysis, and advanced deep learning-based protein structure prediction tool Alphafold2, we identified an evolutionary processes in which a conserved cold-active-like motif is presence in a distinct subclade of the tree and further predicted and simulated the three-dimensional structure of a putative cold-active lipase with the cold active motif, Glalip03, from Glaciozyma antarctica PI12. Molecular dynamics at low temperatures have revealed global stability over a wide range of temperatures, flexibility, and the ability to cope with changes in water and solvent entropy. Therefore, the knowledge we uncover here will be crucial for future research into how these low-temperature-adapted enzymes maintain their overall flexibility and function at lower temperatures.