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The origin and evolution of ribonucleotide reduction.

Lundin D, Berggren G, Logan DT, Sjöberg BM - Life (Basel) (2015)

Bottom Line: Ribonucleotide reduction is the only pathway for de novo synthesis of deoxyribonucleotides in extant organisms.This chemically demanding reaction, which proceeds via a carbon-centered free radical, is catalyzed by ribonucleotide reductase (RNR).While it is entirely possible that a different pathway was later replaced with the modern mechanism, here we explore the evolutionary and biochemical limits for an origin of the mechanism in the RNA + protein world and suggest a model for a prototypical ribonucleotide reductase (protoRNR).

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, SE-106 91 Stockholm, Sweden. daniel.lundin@scilifelab.se.

ABSTRACT
Ribonucleotide reduction is the only pathway for de novo synthesis of deoxyribonucleotides in extant organisms. This chemically demanding reaction, which proceeds via a carbon-centered free radical, is catalyzed by ribonucleotide reductase (RNR). The mechanism has been deemed unlikely to be catalyzed by a ribozyme, creating an enigma regarding how the building blocks for DNA were synthesized at the transition from RNA- to DNA-encoded genomes. While it is entirely possible that a different pathway was later replaced with the modern mechanism, here we explore the evolutionary and biochemical limits for an origin of the mechanism in the RNA + protein world and suggest a model for a prototypical ribonucleotide reductase (protoRNR). From the protoRNR evolved the ancestor to modern RNRs, the urRNR, which diversified into the modern three classes. Since the initial radical generation differs between the three modern classes, it is difficult to establish how it was generated in the urRNR. Here we suggest a model that is similar to the B12-dependent mechanism in modern class II RNRs.

No MeSH data available.


Histograms of alignment to sequence length ratios (x-axes) between the catalytic components of the three RNR classes (NrdA: class I, NrdJ: class II and NrdD: class III). Sequences from the catalytic subunit of all three RNR classes were aligned to each other, within and between classes, using the LAST aligner [77]. In each diagram, the first mentioned enzyme was used as query and the second as target. The different length distributions in the three classes makes the “mirror” diagrams—when a class is used as query and target, respectively—slightly different from each other.
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life-05-00604-f008: Histograms of alignment to sequence length ratios (x-axes) between the catalytic components of the three RNR classes (NrdA: class I, NrdJ: class II and NrdD: class III). Sequences from the catalytic subunit of all three RNR classes were aligned to each other, within and between classes, using the LAST aligner [77]. In each diagram, the first mentioned enzyme was used as query and the second as target. The different length distributions in the three classes makes the “mirror” diagrams—when a class is used as query and target, respectively—slightly different from each other.

Mentions: Overall sequence similarity between RNR classes is generally low, here quantified as the ratio of length of best pairwise alignment to length of full sequence (Figure 8). Between classes, class I and II (Figure 8, panels NrdA-J and NrdJ-A) are more similar to each other than either is to class III (Figure 8, panels NrdA-D and NrdJ-D), suggesting the former are more closely related to each other than to class III. Both class I and class III have high within-class similarities but, interestingly, class II does not (Figure 8, panels on the diagonal NrdA-A, NrdD-D and NrdJ-J). The bimodal distribution of sequence similarities in class II is caused by the emergence of the monomeric class II subclass with a dimer-mimicking insertion of 130 amino acids that interrupts alignments [39] (Section 4.3.1).


The origin and evolution of ribonucleotide reduction.

Lundin D, Berggren G, Logan DT, Sjöberg BM - Life (Basel) (2015)

Histograms of alignment to sequence length ratios (x-axes) between the catalytic components of the three RNR classes (NrdA: class I, NrdJ: class II and NrdD: class III). Sequences from the catalytic subunit of all three RNR classes were aligned to each other, within and between classes, using the LAST aligner [77]. In each diagram, the first mentioned enzyme was used as query and the second as target. The different length distributions in the three classes makes the “mirror” diagrams—when a class is used as query and target, respectively—slightly different from each other.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4390871&req=5

life-05-00604-f008: Histograms of alignment to sequence length ratios (x-axes) between the catalytic components of the three RNR classes (NrdA: class I, NrdJ: class II and NrdD: class III). Sequences from the catalytic subunit of all three RNR classes were aligned to each other, within and between classes, using the LAST aligner [77]. In each diagram, the first mentioned enzyme was used as query and the second as target. The different length distributions in the three classes makes the “mirror” diagrams—when a class is used as query and target, respectively—slightly different from each other.
Mentions: Overall sequence similarity between RNR classes is generally low, here quantified as the ratio of length of best pairwise alignment to length of full sequence (Figure 8). Between classes, class I and II (Figure 8, panels NrdA-J and NrdJ-A) are more similar to each other than either is to class III (Figure 8, panels NrdA-D and NrdJ-D), suggesting the former are more closely related to each other than to class III. Both class I and class III have high within-class similarities but, interestingly, class II does not (Figure 8, panels on the diagonal NrdA-A, NrdD-D and NrdJ-J). The bimodal distribution of sequence similarities in class II is caused by the emergence of the monomeric class II subclass with a dimer-mimicking insertion of 130 amino acids that interrupts alignments [39] (Section 4.3.1).

Bottom Line: Ribonucleotide reduction is the only pathway for de novo synthesis of deoxyribonucleotides in extant organisms.This chemically demanding reaction, which proceeds via a carbon-centered free radical, is catalyzed by ribonucleotide reductase (RNR).While it is entirely possible that a different pathway was later replaced with the modern mechanism, here we explore the evolutionary and biochemical limits for an origin of the mechanism in the RNA + protein world and suggest a model for a prototypical ribonucleotide reductase (protoRNR).

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Biophysics, Arrhenius Laboratories, Stockholm University, SE-106 91 Stockholm, Sweden. daniel.lundin@scilifelab.se.

ABSTRACT
Ribonucleotide reduction is the only pathway for de novo synthesis of deoxyribonucleotides in extant organisms. This chemically demanding reaction, which proceeds via a carbon-centered free radical, is catalyzed by ribonucleotide reductase (RNR). The mechanism has been deemed unlikely to be catalyzed by a ribozyme, creating an enigma regarding how the building blocks for DNA were synthesized at the transition from RNA- to DNA-encoded genomes. While it is entirely possible that a different pathway was later replaced with the modern mechanism, here we explore the evolutionary and biochemical limits for an origin of the mechanism in the RNA + protein world and suggest a model for a prototypical ribonucleotide reductase (protoRNR). From the protoRNR evolved the ancestor to modern RNRs, the urRNR, which diversified into the modern three classes. Since the initial radical generation differs between the three modern classes, it is difficult to establish how it was generated in the urRNR. Here we suggest a model that is similar to the B12-dependent mechanism in modern class II RNRs.

No MeSH data available.