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Origin and Functionality of Prokaryotic-Like dCTP Deaminases and Thymidylate Synthase in Eukaryotic Social Amoebae
The de novo synthesis of dTTP uses several pathways. Gram-negative bacteria use dCTP deaminase (Dcd) to convert dCTP into dUTP, whereas eukaryotes and Gram-positive bacteria instead use dCMP deaminase to transform dCMP to dUMP. Surprisingly, a eukaryote Dictyostelium discoideum has, in addition to dCMP deaminases, two dCTP deaminases (Dcd1Dicty and Dcd2Dicty). Expression of either DcdDicty fully rescued the slow growth of an Escherichia coli dcd knockout. Both DcdDicty proteins mitigated the hydroxyurea sensitivity of a Schizosaccharomyces pombe dCMP deaminase knockout. Phylogenetic analysis showed that dcd1Dicty homologs may have entered the common ancestor of the eukaryotic groups of Amoebozoa, Obazoa, Metamonada, and Discoba through an ancient horizontal gene transfer (HGT) from a prokaryote, or an ancient endosymbiotic gene transfer (EGT) from a mitochondrion, followed by HGT from Amoebozoa to several other unrelated groups of eukaryotes. In contrast, the dcd2Dicty homologs were derived from separate HGT events from a prokaryote or a virus into either Amoebozoa or Rhizaria, followed by an HGT between them. ThyXDicty, the D. discoideum thymidylate synthase (TS), another enzyme of the dTTP biosynthesis pathway, was suggested previously to be acquired from the ancestral mitochondria or by HGT from alpha-proteobacteria. ThyXDicty can fully rescue the E. coli TS knockout. Our phylogenetic analysis concluded that thyXDicty was obtained by the common ancestor of social amoebae not from mitochondria but from a bacterium. Both HGT and EGT appear to have contributed to the enzyme diversity of the dTTP synthesis pathway in most social amoebae, many Amoebozoa, and other eukaryotes.
Liang, Heng, "Origin and Functionality of Prokaryotic-Like dCTP Deaminases and Thymidylate Synthase in Eukaryotic Social Amoebae" (2023). ETD collection for University of Nebraska-Lincoln. AAI30814347.