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-dependentisocitrate dehydrogenase for humans, mice, and two species of voles(Microtus mexicanus and Microtus ochrogaster). Inferred amino acidsequences from these taxa display a high level of amino acid sequenceconservation, comparable to that of myosin beta heavy chain, and shareknown structural features. A Caenorhabditis elegans enzyme that waspreviously identified as a protein similar to isocitrate dehydrogenase ismost likely the NADP-dependent cytosolic isocitrate dehydrogenase enzymeequivalent, based on amino acid similarity to mammalian enzymes andphylogenetic analysis. We also suggest that NADP-dependent isocitratedehydrogenases characterized from alfalfa, soybean, and eucalyptus are mostlikely cytosolic enzymes. The phylogenetic tree of various isocitratedehydrogenases from eukaryotic sources revealed that independent geneduplications may have given rise to the cytosolic and mitochondrial formsof NADP-dependent isocitrate dehydrogenase in animals and fungi. Thereappears to be no statistical support for a hypothesis that themitochondrial and cytosolic forms of the enzyme are orthologous in thesegroups. A possible scenario of the evolution of NADP-dependent isocitratedehydrogenases is proposed.