Kondrashov FA et al. (2006), Evolution of glyoxylate cycle enzymes in Metazo...

ECB-ART-50834

Biol Direct 2006 Oct 23;1:31. doi: 10.1186/1745-6150-1-31.

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Evolution of glyoxylate cycle enzymes in Metazoa: evidence of multiple horizontal transfer events and pseudogene formation.

Kondrashov FA , Koonin EV , Morgunov IG , Finogenova TV , Kondrashova MN .

Abstract
BACKGROUND: The glyoxylate cycle is thought to be present in bacteria, protists, plants, fungi, and nematodes, but not in other Metazoa. However, activity of the glyoxylate cycle enzymes, malate synthase (MS) and isocitrate lyase (ICL), in animal tissues has been reported. In order to clarify the status of the MS and ICL genes in animals and get an insight into their evolution, we undertook a comparative-genomic study. RESULTS: Using sequence similarity searches, we identified MS genes in arthropods, echinoderms, and vertebrates, including platypus and opossum, but not in the numerous sequenced genomes of placental mammals. The regions of the placental mammals' genomes expected to code for malate synthase, as determined by comparison of the gene orders in vertebrate genomes, show clear similarity to the opossum MS sequence but contain stop codons, indicating that the MS gene became a pseudogene in placental mammals. By contrast, the ICL gene is undetectable in animals other than the nematodes that possess a bifunctional, fused ICL-MS gene. Examination of phylogenetic trees of MS and ICL suggests multiple horizontal gene transfer events that probably went in both directions between several bacterial and eukaryotic lineages. The strongest evidence was obtained for the acquisition of the bifunctional ICL-MS gene from an as yet unknown bacterial source with the corresponding operonic organization by the common ancestor of the nematodes. CONCLUSION: The distribution of the MS and ICL genes in animals suggests that either they encode alternative enzymes of the glyoxylate cycle that are not orthologous to the known MS and ICL or the animal MS acquired a new function that remains to be characterized. Regardless of the ultimate solution to this conundrum, the genes for the glyoxylate cycle enzymes present a remarkable variety of evolutionary events including unusual horizontal gene transfer from bacteria to animals.

PubMed ID: 17059607
PMC ID: PMC1630690
Article link: Biol Direct

Article Images: [+] show captions

	Figure 1. The complete Krebs, truncated Krebs and glyoxylate cycles. Abbreviations: α-ketoglytarate -KGL, α-ketoglytarate dehydrogenase – KGDH, acetyl-CoA – Ac-CoA, aspartate – ASP, citrate-CIT, gluconeogenesis – GNG, glutamate – GLU, glycogene – GLYC, glyoxylate-Glyox, isocitrate – ISC, isocitrate lyase – ICL, malate-MAL, malate synthase – MS, oxalacetate – OAA, phosphoenolpyruvate – PEP, succinate-SUC, transaminases (aminotransferases) – TRAM. The truncated Krebs cycle includes the OAA + GLU -> ASP + KGL reaction that is catalyzed by glutamate-glyoxylate-aminotransferase [58, 59]. TRAM reactions in mitochondria and cytosol are connected by common amino and keto acids. Thick lines represent rapid reaction steps, dashed lines – slow and easily inhibited steps, crossed out like is the blocked aconitase reaction, dotted like – malate synthase pathway that may have been recently lost in placental mammal common ancestor.
	Figure 2. The syntenic region around malate synthase orthologs in completely sequenced Coelomate genomes.
	Figure 3. The phylogenies of isocitrate lyase (a) and malate synthase (b). The tree was constructed using the Bayesian approach with the posterior probabilities shown on the tree. Posterior probabilities of 1.0 are not shown.
	Figure 4. Multiple alignment of isocitrate lyase in the vicinity of the plant- and fungal-specific insertion.
	Figure 5. The inferred scenario for ICL and MS during eukaryotic evolution. The schematic shows only selected branches of the phylogenetic tree of eukaryotes, those that are relevant to inferred events in the evolution of the glyoxylate cycle. Block arrows show horizontal gene transfer, and crosses show gene loss; MSP stands for malate synthase pseudogene.
	Figure 6. Multiple alignment of malate synthase in the vicinity of the intron common to higher animals and plants. The presence of an intron is shown with the carrot symbol (^) while the absence of one is shown with an underscore (_).

References [+] :

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