Abstract:DNA gyrase is a type II topoisomerase with the unique capacity to introduce negative supercoiling in DNA. In bacteria, DNA gyrase has an essential role in the homeostatic regulation of supercoiling. While ubiquitous in Bacteria, DNA gyrase was previously reported to have a patchy distribution in Archaea but its emergent function and evolutionary history in this domain of life remains elusive. In this study, we used phylogenomic approaches and an up-to date sequence dataset to establish global and archaea-speci… Show more
“…4 , middle inset “MCM helicase”). This latter result is also in agreement with the placements of the Asgard sequences in the B-family DNA Polymerase 30 and DNA Gyrase 31 phylogenies for which the Asgard form monophyletic groups with other archaeal sequences. Fig.…”
Asgard archaea include the closest known archaeal relatives of eukaryotes. Here, we investigate the evolution and function of Asgard thymidylate synthases and other folate-dependent enzymes required for the biosynthesis of DNA, RNA, amino acids and vitamins, as well as syntrophic amino acid utilization. Phylogenies of Asgard folate-dependent enzymes are consistent with their horizontal transmission from various bacterial groups. We experimentally validate the functionality of thymidylate synthase ThyX of the cultured ‘Candidatus Prometheoarchaeum syntrophicum’. The enzyme efficiently uses bacterial-like folates and is inhibited by mycobacterial ThyX inhibitors, even though the majority of experimentally tested archaea are known to use carbon carriers distinct from bacterial folates. Our phylogenetic analyses suggest that the eukaryotic thymidylate synthase, required for de novo DNA synthesis, is not closely related to archaeal enzymes and might have been transferred from bacteria to protoeukaryotes during eukaryogenesis. Altogether, our study suggests that the capacity of eukaryotic cells to duplicate their genetic material is a sum of archaeal (replisome) and bacterial (thymidylate synthase) characteristics. We also propose that recent prevalent lateral gene transfer from bacteria has markedly shaped the metabolism of Asgard archaea.
“…4 , middle inset “MCM helicase”). This latter result is also in agreement with the placements of the Asgard sequences in the B-family DNA Polymerase 30 and DNA Gyrase 31 phylogenies for which the Asgard form monophyletic groups with other archaeal sequences. Fig.…”
Asgard archaea include the closest known archaeal relatives of eukaryotes. Here, we investigate the evolution and function of Asgard thymidylate synthases and other folate-dependent enzymes required for the biosynthesis of DNA, RNA, amino acids and vitamins, as well as syntrophic amino acid utilization. Phylogenies of Asgard folate-dependent enzymes are consistent with their horizontal transmission from various bacterial groups. We experimentally validate the functionality of thymidylate synthase ThyX of the cultured ‘Candidatus Prometheoarchaeum syntrophicum’. The enzyme efficiently uses bacterial-like folates and is inhibited by mycobacterial ThyX inhibitors, even though the majority of experimentally tested archaea are known to use carbon carriers distinct from bacterial folates. Our phylogenetic analyses suggest that the eukaryotic thymidylate synthase, required for de novo DNA synthesis, is not closely related to archaeal enzymes and might have been transferred from bacteria to protoeukaryotes during eukaryogenesis. Altogether, our study suggests that the capacity of eukaryotic cells to duplicate their genetic material is a sum of archaeal (replisome) and bacterial (thymidylate synthase) characteristics. We also propose that recent prevalent lateral gene transfer from bacteria has markedly shaped the metabolism of Asgard archaea.
“…The long branch between Archaea and Bacteria first observed by Carl Woese in the rRNA tree was in fact also recovered long ago in universal protein trees (for a review, see Refs. 23 , 57 ) and confirmed recently by several authors using extensive genomic data, both for ribosomal and for non‐ribosomal proteins 22 , 48 , 49 . Long branch lengths between these two domains should be a major criterion in determining which universal protein was indeed present in LUCA, besides widespread distribution within each of the two domains 48 , 58 .…”
Section: Challenges To Carl Woese's Legacysupporting
confidence: 64%
“…The long branch between Archaea and Bacteria first observed by Carl Woese in the rRNA tree was in fact also recovered long ago in universal protein trees (for a review, see Refs 23,57 22,48,49 .…”
Section: Challenges To Carl Woese's Legacymentioning
“…The roles of topoisomerases in DNA topology regulation in Archaea should differ from Bacteria based on the topoisomerases present [ 29 ]. Gyrase activity is not always present in Archaea [ 110 ], and no type IA Topo I with robust relaxation activity has been identified in Archaea. The type IIB Topo VI present in archaeal species is capable of relaxing both positive and negative supercoils, in addition to possessing decatenase activity [ 29 , 111 ].…”
Section: Physiological Functions Of Type Ia Topoisomerasesmentioning
Topoisomerases regulate the topological state of cellular genomes to prevent impediments to vital cellular processes, including replication and transcription from suboptimal supercoiling of double-stranded DNA, and to untangle topological barriers generated as replication or recombination intermediates. The subfamily of type IA topoisomerases are the only topoisomerases that can alter the interlinking of both DNA and RNA. In this article, we provide a review of the mechanisms by which four highly conserved N-terminal protein domains fold into a toroidal structure, enabling cleavage and religation of a single strand of DNA or RNA. We also explore how these conserved domains can be combined with numerous non-conserved protein sequences located in the C-terminal domains to form a diverse range of type IA topoisomerases in Archaea, Bacteria, and Eukarya. There is at least one type IA topoisomerase present in nearly every free-living organism. The variation in C-terminal domain sequences and interacting partners such as helicases enable type IA topoisomerases to conduct important cellular functions that require the passage of nucleic acids through the break of a single-strand DNA or RNA that is held by the conserved N-terminal toroidal domains. In addition, this review will exam a range of human genetic disorders that have been linked to the malfunction of type IA topoisomerase.
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