Genetic evidence for a novel thymidylate synthase in the halophilic archaeon<i>Halobacterium salinarum</i>and in<i>Campylobacter jejuni</i>

Giladi, Moshe; Bitan-Banin, Gili; Mevarech, Moshe; Ortenberg, Ron

doi:10.1111/j.1574-6968.2002.tb11422.x

Cited by 37 publications

(15 citation statements)

References 10 publications

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“…In agreement with this proposal, thyX from Campylobacter jejuni was found to complement an Escherichia coli thyA strain only under microaerophilic conditions [9]. In the light of modern biosynthetic pathways for pyrimidine compounds, uracil-containing DNA (U-DNA) has probably served as an intermediate during the transition from the RNA to the DNA world [10].…”

Section: Phylogenetic Distributions Of Thymidylate Synthases In the Mmentioning

confidence: 78%

Two distinct pathways for thymidylate (dTMP) synthesis in (hyper)thermophilic Bacteria and Archaea

Leduc

Graziani

Meslet‐Cladière

et al. 2004

Biochemical Society Transactions

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The hyperthermophilic anaerobic archaeon Pyrococcus abyssi, which lacks thymidine kinase, incorporates label from extracellular uracil, but not from thymidine, into its DNA. This implies that P. abyssi must synthesize dTMP (thymidylate), an essential precursor for DNA synthesis, de novo. However, iterative similarity searches of the three completed Pyrococcus genomes fail to detect candidate genes for canonical thymidylate synthase ThyA, suggesting the presence of alternative pathways for dTMP synthesis. Indeed, by identifying a novel class of flavin-dependent thymidylate synthases, ThyX, we have recently proven that two distinct pathways for de novo synthesis of dTMP are operational in the microbial world. While both thyX and thyA can be found in hyperthermophilic micro-organisms, the phylogenetic distribution of thyX among hyperthermophiles is wider than that of thyA. In this contribution, we discuss the differences in the distinct mechanisms of dTMP synthesis, with a special emphasis on hyperthermophilic micro-organisms.

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Section: Phylogenetic Distributions Of Thymidylate Synthases In the Mmentioning

confidence: 78%

Two distinct pathways for thymidylate (dTMP) synthesis in (hyper)thermophilic Bacteria and Archaea

Leduc

Graziani

Meslet‐Cladière

et al. 2004

Biochemical Society Transactions

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“…Several alternatives come to mind: 1) for a subset of pathogens, joint expression of thyX and thyA may not affect their fitness when free living but could contribute to the virulence of their interaction with the host; 2) the availability of 2 distinct genes will ensure constitutive formation of thymidine when one of the enzymes cannot function properly due to the presence of inhibiting analogs (Santi and McHenry 1972; Costi et al 2005); and 3) in environments with oxygen-limiting conditions, thyX and thyA are differentially expressed, thus enhancing survivability (Giladi et al 2002). In this context, the question for which bacteria the encoding of both enzymes constitutes one of the selective benefits listed above is currently unknown.…”

Section: Resultsmentioning

confidence: 99%

An Evolutionary Analysis of Lateral Gene Transfer in Thymidylate Synthase Enzymes

et al. 2010

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Thymidylate synthases (Thy) are key enzymes in the synthesis of deoxythymidylate, 1 of the 4 building blocks of DNA. As such, they are essential for all DNA-based forms of life and therefore implicated in the hypothesized transition from RNA genomes to DNA genomes. Two evolutionally unrelated Thy enzymes, ThyA and ThyX, are known to catalyze the same biochemical reaction. Both enzymes are sporadically distributed within each of the 3 domains of life in a pattern that suggests multiple nonhomologous lateral gene transfer (LGT) events. We present a phylogenetic analysis of the evolution of the 2 enzymes, aimed at unraveling their entangled evolutionary history and tracing their origin back to early life. A novel probabilistic evolutionary model was developed, which allowed us to compute the posterior probabilities and the posterior expectation of the number of LGT events. Simulation studies were performed to validate the model's ability to accurately detect LGT events, which have occurred throughout a large phylogeny. Applying the model to the Thy data revealed widespread nonhomologous LGT between and within all 3 domains of life. By reconstructing the ThyA and ThyX gene trees, the most likely donor of each LGT event was inferred. The role of viruses in LGT of Thy is finally discussed.

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“…salinarum and Haloarcula marismortui that encode enzymes for an alternative pathway for reduced folate biosynthesis. Prior to the study, these genes had no known function [95, 96]. Recently, the biological function of a gene annotated as fabG1 , which is one of six fabG paralogs of Haloarcula hispanica , was clarified [97].…”

Section: Genetics: Application Of Hfx Volcanii As a “Natural Nullmentioning

confidence: 99%

Functional Genomic and Advanced Genetic Studies Reveal Novel Insights into the Metabolism, Regulation, and Biology ofHaloferax volcanii

Soppa

2011

Archaea

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The genome sequence of Haloferax volcanii is available and several comparative genomic in silico studies were performed that yielded novel insight for example into protein export, RNA modifications, small non-coding RNAs, and ubiquitin-like Small Archaeal Modifier Proteins. The full range of functional genomic methods has been established and results from transcriptomic, proteomic and metabolomic studies are discussed. Notably, Hfx. volcanii is together with Halobacterium salinarum the only prokaryotic species for which a translatome analysis has been performed. The results revealed that the fraction of translationally-regulated genes in haloarchaea is as high as in eukaryotes. A highly efficient genetic system has been established that enables the application of libraries as well as the parallel generation of genomic deletion mutants. Facile mutant generation is complemented by the possibility to culture Hfx. volcanii in microtiter plates, allowing the phenotyping of mutant collections. Genetic approaches are currently used to study diverse biological questions–from replication to posttranslational modification—and selected results are discussed. Taken together, the wealth of functional genomic and genetic tools make Hfx. volcanii a bona fide archaeal model species, which has enabled the generation of important results in recent years and will most likely generate further breakthroughs in the future.

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Genetic evidence for a novel thymidylate synthase in the halophilic archaeonHalobacterium salinarumand inCampylobacter jejuni

Cited by 37 publications

References 10 publications

Two distinct pathways for thymidylate (dTMP) synthesis in (hyper)thermophilic Bacteria and Archaea

Two distinct pathways for thymidylate (dTMP) synthesis in (hyper)thermophilic Bacteria and Archaea

An Evolutionary Analysis of Lateral Gene Transfer in Thymidylate Synthase Enzymes

Functional Genomic and Advanced Genetic Studies Reveal Novel Insights into the Metabolism, Regulation, and Biology ofHaloferax volcanii

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