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The functional diversity and evolutionary relationships of ferritin-like proteins
Stockholm University, Faculty of Science, Department of Molecular Biology and Functional Genomics.
Stockholm University, Faculty of Science, Department of Molecular Biology and Functional Genomics.
Stockholm University, Faculty of Science, Department of Molecular Biology and Functional Genomics.
Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
(English)Manuscript (preprint) (Other academic)
Abstract [en]

BackgroundThe ferritin-like proteins are evolutionarily related, as evidenced by the topology oftheir signature metal-binding four-helix bundle. They perform diverse functions suchas iron/oxygen detoxification, iron storage, DNA protection and substrate oxidation.Though evolutionarily related, sequence similarity between families and often withinfamilies is low. To analyse the evolutionary relationships between individual familiesand their functional roles systematically, we turned to 3D structural alignment andphylogenetic methods.ResultsOur phylogenetic network recovers all characterised functional groups of ferritin-likeproteins and suggests evolutionary relationships between them. The evolutionaryhypotheses that are suggested by the phylogeny are tested against availableindependent evidence such as dimerisation geometries, qualitative comparison ofstructures and sequence based partial phylogenies. Generally our hypotheses stand upagainst the evidence, but in a few cases verification have to await further data.ConclusionsTwo large evolutionary groups of ferritin-like proteins are identified from structuralphylogeny: ferritins, bacterioferritins and Dps proteins on one hand, and substrateoxidising proteins, bacterial multicomponent monooxygenases, fatty acid desaturasesand class I ribonucleotide reductase radical generating subunits, on the other. Themethod we present provides a robust way of evolutionarily classifying a functionallydiverse group of distantly related proteins, as well as examining the possible functionsof poorly-characterised proteins.

National Category
Biochemistry and Molecular Biology
Research subject
Molecular Biology
Identifiers
URN: urn:nbn:se:su:diva-43636OAI: oai:DiVA.org:su-43636DiVA: diva2:358739
Available from: 2010-10-25 Created: 2010-10-25 Last updated: 2012-01-17Bibliographically 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.
Keyword
Evolution, ribonucleotide reductase, horizontal gene transfer, phylogeny, protein classification
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Biology
Identifiers
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)
Opponent
Supervisors
Note
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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