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

Anton Nekrutenko, * David M. Hillis, John C. Patton,* Robert D. Bradley,* and Robert J. Baker*

* Department of Biological Sciences, Texas Tech University

Department of Zoology and Institute of Cellular and Molecular Biology, University of Texas at Austin

Abstract. In this study, we report cDNA sequences of the cytosolic NADP-dependent isocitrate dehydrogenase for humans, mice, and two species of voles (Microtus mexicanus and Microtus ochrogaster). Inferred amino acid sequences from these taxa display high level of amino acid sequence conservation, comparable to that of myosin β heavy chain, and share known structural features. A Caenorhabditis elegans enzyme that was previously identified as a protein similar to isocitrate dehydrogenase is most likely the NADP-dependent cytosolic isocitrate dehydrogenase enzyme equivalent, based on amino acid similarity to mammalian enzymes and phylogenetic analysis. We also suggest that NADP-dependent cytosolic isocitrate dehydrogenases characterized from alfalfa, soybean, 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 mitochondrial forms of NADP-dependent cytosolic isocitrate dehydrogenase in animals and fungi. There appears to be no statistical support for a hypothesis that the mitochondrial and cytosolic forms of enzyme are orthologous in these groups. A possible scenario of the evolution of NADP-dependent cytosolic isocitrate dehydrogenases is proposed.