Evolution of the enzymes of the citric acid cycle and the glyoxylate cycle of higher plants. A case study of endosymbiotic gene transfer

Eur J Biochem. 2002 Feb;269(3):868-83. doi: 10.1046/j.0014-2956.2001.02722.x.


The citric acid or tricarboxylic acid cycle is a central element of higher-plant carbon metabolism which provides, among other things, electrons for oxidative phosphorylation in the inner mitochondrial membrane, intermediates for amino-acid biosynthesis, and oxaloacetate for gluconeogenesis from succinate derived from fatty acids via the glyoxylate cycle in glyoxysomes. The tricarboxylic acid cycle is a typical mitochondrial pathway and is widespread among alpha-proteobacteria, the group of eubacteria as defined under rRNA systematics from which mitochondria arose. Most of the enzymes of the tricarboxylic acid cycle are encoded in the nucleus in higher eukaryotes, and several have been previously shown to branch with their homologues from alpha-proteobacteria, indicating that the eukaryotic nuclear genes were acquired from the mitochondrial genome during the course of evolution. Here, we investigate the individual evolutionary histories of all of the enzymes of the tricarboxylic acid cycle and the glyoxylate cycle using protein maximum likelihood phylogenies, focusing on the evolutionary origin of the nuclear-encoded proteins in higher plants. The results indicate that about half of the proteins involved in this eukaryotic pathway are most similar to their alpha-proteobacterial homologues, whereas the remainder are most similar to eubacterial, but not specifically alpha-proteobacterial, homologues. A consideration of (a) the process of lateral gene transfer among free-living prokaryotes and (b) the mechanistics of endosymbiotic (symbiont-to-host) gene transfer reveals that it is unrealistic to expect all nuclear genes that were acquired from the alpha-proteobacterial ancestor of mitochondria to branch specifically with their homologues encoded in the genomes of contemporary alpha-proteobacteria. Rather, even if molecular phylogenetics were to work perfectly (which it does not), then some nuclear-encoded proteins that were acquired from the alpha-proteobacterial ancestor of mitochondria should, in phylogenetic trees, branch with homologues that are no longer found in most alpha-proteobacterial genomes, and some should reside on long branches that reveal affinity to eubacterial rather than archaebacterial homologues, but no particular affinity for any specific eubacterial donor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aconitate Hydratase / physiology
  • Citrate (si)-Synthase / physiology
  • Citric Acid Cycle*
  • Enzymes / physiology*
  • Evolution, Molecular*
  • Fumarate Hydratase / physiology
  • Glyoxylates / metabolism*
  • Isocitrate Dehydrogenase / physiology
  • Isocitrate Lyase / physiology
  • Ketone Oxidoreductases / physiology
  • Malate Dehydrogenase / physiology
  • Malate Synthase / physiology
  • Phylogeny
  • Plants / metabolism*
  • Succinate Dehydrogenase / physiology


  • Enzymes
  • Glyoxylates
  • Malate Dehydrogenase
  • Isocitrate Dehydrogenase
  • Ketone Oxidoreductases
  • pyruvate dehydrogenase (NADP+)
  • Succinate Dehydrogenase
  • Citrate (si)-Synthase
  • Malate Synthase
  • Isocitrate Lyase
  • Fumarate Hydratase
  • Aconitate Hydratase
  • glyoxylic acid