title: Evolution of bacterial phosphoglycerate mutases: non-homologous isofunctional enzymes undergoing gene losses, gains and lateral transfers.
abstract: BACKGROUND
  The glycolytic phosphoglycerate mutases exist as non-homologous isofunctional enzymes (NISE) having independent evolutionary origins and no similarity in primary sequence, 3D structure, or catalytic mechanism. Cofactor-dependent PGM (dPGM) requires 2,3-bisphosphoglycerate for activity; cofactor-independent PGM (iPGM) does not. The PGM profile of any given bacterium is unpredictable and some organisms such as Escherichia coli encode both forms.
  
  
  RESULTS
  To examine the distribution of PGM NISE throughout the Bacteria, and gain insight into the evolutionary processes that shape their phyletic profiles, we searched bacterial genome sequences for the presence of dPGM and iPGM. Both forms exhibited patchy distributions throughout the bacterial domain. Species within the same genus, or even strains of the same species, frequently differ in their PGM repertoire. The distribution is further complicated by the common occurrence of dPGM paralogs, while iPGM paralogs are rare. Larger genomes are more likely to accommodate PGM paralogs or both NISE forms. Lateral gene transfers have shaped the PGM profiles with intradomain and interdomain transfers apparent. Archaeal-type iPGM was identified in many bacteria, often as the sole PGM. To address the function of PGM NISE in an organism encoding both forms, we analyzed recombinant enzymes from E. coli. Both NISE were active mutases, but the specific activity of dPGM greatly exceeded that of iPGM, which showed highest activity in the presence of manganese. We created PGM null mutants in E. coli and discovered the ΔdPGM mutant grew slowly due to a delay in exiting stationary phase. Overexpression of dPGM or iPGM overcame this defect.
  
  
  CONCLUSIONS
  Our biochemical and genetic analyses in E. coli firmly establish dPGM and iPGM as NISE. Metabolic redundancy is indicated since only larger genomes encode both forms. Non-orthologous gene displacement can fully account for the non-uniform PGM distribution we report across the bacterial domain.
authors.affiliation: Division of Parasitology, New England Biolabs, Inc, Ipswich, Massachusetts, United States of America. foster@neb.com
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Foster
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Davis
authors.forename: Sylvine
authors.initials: S
authors.lastname: Raverdy
authors.forename: Marion H
authors.initials: MH
authors.lastname: Sibley
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Raleigh
authors.forename: Sanjay
authors.initials: S
authors.lastname: Kumar
authors.forename: Clotilde K S
authors.initials: CK
authors.lastname: Carlow
mesh_terms: D001419:Bacteria / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D019143:Evolution, Molecular; D022761:Gene Transfer, Horizontal; D005816:Genetic Complementation Test; D020745:Genome, Archaeal; D016680:Genome, Bacterial; D010735:Phosphoglycerate Kinase / Q000235:genetics*; D013045:Species Specificity
chemical_list: D010735:Phosphoglycerate Kinase