title: Flavin-dependent thymidylate synthase X limits chromosomal DNA replication.
abstract: We have investigated the hitherto unexplored possibility that differences in the catalytic efficiencies of thymidylate synthases ThyX and ThyA, enzymes that produce the essential DNA precursor dTMP, have influenced prokaryotic genome evolution. We demonstrate that DNA replication speed in bacteria and archaea that contain the low-activity ThyX enzyme is up to 10-fold decreased compared with species that contain the catalytically more efficient ThyA. Our statistical studies of >400 genomes indicated that ThyA proteins are preferred for the replication of large genomes, providing further evidence that the thymidylate metabolism is limiting expansion of prokaryotic genomes. Because both ThyX and ThyA participate in frequent reciprocal gene replacement events, our observations indicate that the bacterial metabolism continues to modulate the size and composition of prokaryotic genomes. We also propose that the increased kinetic efficiency of thymidylate synthesis has contributed to extending the prokaryotic evolutionary potential.
authors.affiliation: Laboratoire d'Optique et Biosciences, Centre National de la Recherche Scientifique, Ecole Polytechnique, F-91128 Palaiseau, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Escartin
authors.forename: Stéphane
authors.initials: S
authors.lastname: Skouloubris
authors.forename: Ursula
authors.initials: U
authors.lastname: Liebl
authors.forename: Hannu
authors.initials: H
authors.lastname: Myllykallio
mesh_terms: D002384:Catalysis; D002876:Chromosomes, Bacterial / Q000235:genetics / Q000378:metabolism; D004261:DNA Replication / Q000235:genetics / Q000502:physiology*; D004269:DNA, Bacterial / Q000235:genetics / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D017353:Gene Deletion; D005798:Genes, Bacterial; D016480:Helicobacter pylori / Q000235:genetics / Q000378:metabolism; D007700:Kinetics; D007780:Lacticaseibacillus casei / Q000201:enzymology / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013940:Thymidylate Synthase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D004269:DNA, Bacterial; D011994:Recombinant Proteins; D005182:Flavin-Adenine Dinucleotide; D013940:Thymidylate Synthase