Cytosolic isocitrate dehydrogenase in humans, mice, and voles and phylogenetic analysis of the enzyme family

In this study, we report cDNA sequences of the cytosolic NADP-dependent iso citrate dehydrogenase for humans, mice, and two species of voles (Microtus mexicanus and Microtus ochrogaster). inferred amino acid sequences from the se taxa display a high level of amino acid sequence conservation, comparabl e to that of myosin beta heavy chain, and share known structural features. A Caenorhabditis: elegans enzyme that was previously identified as a protei n similar to isocitrate dehydrogenase is most likely the NADP-dependent cyt osolic isocitrate dehydrogenase enzyme equivalent, based on amino acid simi larity to mammalian enzymes and phylogenetic analysis. We also suggest that NADP-dependent isocitrate dehydrogenases characterized from alfalfa, soybe an, and eucalyptus are most likely cytosolic enzymes. The phylogenetic tree of various isocitrate dehydrogenases from eukaryotic sources revealed that independent gene duplications may have given rise to the cytosolic and mit ochondrial forms of NADP-dependent isocitrate dehydrogenase in animals and fungi. There appears to be no statistical support for a hypothesis that the mitochondrial and cytosolic forms of the enzyme are orthologous in these g roups. A possible scenario of the evolution of NADP-dependent isocitrate de hydrogenases is proposed.