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Ribonucleotide reduction: horizontal transfer of a required function spans all three domains
Stockholm University, Faculty of Science, Department of Molecular Biology and Functional Genomics.
Unite Biologie Moléculaire du Gène chez les Extremophiles (BMGE), Departement de Microbiologie, Institut Pasteur, Paris, France.
Institute for Bioengineering of Catalonia (IBEC), Scientific Park of Barcelona, Barcelona, Spain.
Stockholm University, Faculty of Science, Department of Molecular Biology and Functional Genomics.
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2010 (English)In: BMC Evolutionary Biology, ISSN 1471-2148, Vol. 10, no 383Article in journal (Other academic) Published
Abstract [en]

Background Ribonucleotide reduction is the only de novo pathway for synthesis ofdeoxyribonucleotides, the building blocks of DNA. The reaction is catalysed byribonucleotide reductases (RNRs), an ancient enzyme family comprised of threeclasses. Each class has distinct operational constraints, and are broadly distributedacross organisms from all three domains, though few class I RNRs have beenidentified in archaeal genomes, and classes II and III likewise appear rare acrosseukaryotes. In this study, we examine whether this distribution is best explained bypresence of all three classes in the Last Universal Common Ancestor (LUCA), or byhorizontal gene transfer (HGT) of RNR genes. We also examine to what extentenvironmental factors may have impacted the distribution of RNR classes.

Results Our phylogenies show that the Last Eukaryotic Common Ancestor (LECA) possesseda class I RNR, but that the eukaryotic class I enzymes are not directly descended fromclass I RNRs in archaea. Instead, our results indicate that archaeal class I RNR geneshave been independently transferred from bacteria on two occasions. While LECApossessed a class I RNR, our trees indicate that this is ultimately bacterial in origin.We also find convincing evidence that eukaryotic class I RNR has been transferred tothe bacteroidetes, providing a stunning example of HGT from eukaryotes back tobacteria. Based on our phylogenies and available genetic and genomic evidence, classII and III RNRs in eukaryotes also appear to have been transferred from bacteria, with subsequent within-domain transfer between distantly-related eukaryotes. Under the three-domains hypothesis the RNR present in the last common ancestor of archaeaand eukaryotes appears, through a process of elimination, to have been a dimeric classII RNR, though limited sampling of eukaryotes precludes a firm conclusion as the data may be equally well accounted for by HGT.

Conclusions Horizontal gene transfer has clearly played an important role in the evolution of theRNR repertoire of organisms from all three domains of life. Our results clearly showthat class I RNRs have spread to archaea and eukaryotes via transfers from thebacterial domain, indicating that class I likely evolved in the bacteria. We find noclear evolutionary trace placing either class II or III RNRs in the LUCA, despite thefact that ribonucleotide reduction is an essential cellular reaction and was pivotal tothe transition from RNA to DNA genomes. Instead, a general pattern emerges whereenvironmental and enzyme operational constraints, especially the presence or absenceof oxygen, coupled with horizontal transmission are major determinants of the RNR repertoire of genomes.

Place, publisher, year, edition, pages
2010. Vol. 10, no 383
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Biology
URN: urn:nbn:se:su:diva-43635DOI: 10.1186/1471-2148-10-383OAI: diva2:358737
Available from: 2010-10-25 Created: 2010-10-25 Last updated: 2011-02-24Bibliographically approved
In thesis
1. The evolution of ribonucleotide reductases
Open this publication in new window or tab >>The evolution of ribonucleotide reductases
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Evolutionen av ribonukleotidreduktas
Abstract [en]

Ribonucleotide reductase (RNR) catalyses the transformation of RNA building blocks, ribonucleotides, to DNA building blocks, deoxyribonucleotides. This is the only extant reaction pathway for de novo synthesis of DNA building blocks and the enzyme is thus necessary for life. RNR is found in all but a few organisms.

There are three classes of RNR, all evolutionarily related. The classification is built on differences in generation of the radical that is central to the reaction. As a consequence, RNR classes have different operational constraints. Class I requires oxygen, while class III is poisoned by oxygen. Class II is independent of oxygen, but dependent on vitamin B12 and, hence, cobalt. This makes RNR interesting from an evolutionary as well as environmental point of view.

RNR must have evolved before the transition from RNA encoded genomes to DNA encoded. The extant radical-based reaction is likely similar to the ancestral reaction, which entails that the ancestral enzyme was a protein and not an RNR.

My results are consistent with both class II and III being present in the last universal common ancestor. Class I RNR evolved later, presumably once oxygen levels had risen. From commonalities in extant RNRs we can reconstruct their last common ancestor as an enzyme that 1) used a transient cysteine-radical in the reaction, 2) reduced all four ribonucleotides, 3) regulated which nucleotide was reduced after binding an effector nucleotide in the dimer interface of the enzyme and 4) had activity regulation through binding of a nucleotide to another part of the enzyme.

The presence of a specific RNR class is likely to influence the environmental range of organisms, which makes horizontal transfer of RNR particularly interesting. Horizontal transfer of RNR genes is widespread, both between closely related organisms and between domains. For instance, all three classes are present in eukaryotes, but likely all three are results of horizontal transfer.

Abstract [sv]

Ribonukleotidreduktas (RNR) katalyserar omvandlingen av RNA-byggstenar, ribonukleotider, till DNA-byggstenar, deoxyribonukleotider. Reaktionsvägen är den enda kända som resulterar i DNA-byggstenar, och RNR är därmed en nödvändigt för alla levande organismer. RNR-gener finns också i stort sett i alla organismer.

Det finns tre klasser av RNR, som alla är evolutionärt besläktade med varandra. Klassindelningen bygger på hur den radikal som är viktig för reaktionen skapas. De olika klasserna är beroende av sin miljö på olika sätt. Klass I kräver syre medan klass III inte tål syre. Klass II är oberoende av syre, men är istället beroende av vitamin B12 och, därmed, kobolt.

RNR måste ha uppstått innan DNA blev den informationsbärande molekylen i organismer. Det ursprungliga RNR-enzymet måste ha varit ett protein, och inte en RNA-molekyl, p.g.a. den fria radikalen i reaktionen.

Enligt mina resultat kan både klass II- och klass III-RNR ha funnits i den gemensamma förfadern till allt cellulärt liv. Klass I-RNR uppstod senare, när atmosfären började innehålla tillräckligt med syre. Utifrån gemensamma egenskaper i dagens RNRer kan vi dra slutsatsen att proteinet som de två klasserna uppstod ur 1) använde en transient cystein-radikal i reaktionen, 2) kunde katalysera reduktionen av alla fyra nukleotider, 3) reglerade vilken som reducerades genom att binda en nukleotid mellan monomererna och 4) att aktiviteten i enzymet reglerades genom bindning av en nukleotid, i en annan del av enzymet.

Förekomsten av en RNR-klass i en organism är troligen en viktig faktor för vilka miljöer den kan trivas i, vilket gör horisontell överföring av RNR-gener extra intressant. Horizontell överföring är vanligt, såväl mellan nära som avlägset besläktade organismer. I eukaryoter t.ex. finns idag alla tre klasser representerade men alla verkar vara resultatet av horisontell överföring.

Place, publisher, year, edition, pages
Stockholm: Department of molecular biology and functional genomics, Stockholm University, 2010. 59 p.
Evolution, ribonucleotide reductase, horizontal gene transfer, phylogeny, protein classification
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Biology
urn:nbn:se:su:diva-43653 (URN)978-91-7447-163-2 (ISBN)
Public defence
2010-12-03, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
At the time of doctoral defence the following papers were unpublished and had a status as follows: Paper nr. 2: Manuscript; Paper nr 3: Manuscript.Available from: 2010-11-11 Created: 2010-10-25 Last updated: 2010-11-15Bibliographically approved

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