1. Biochemistry and Chemical Biology
  2. Evolutionary Biology

Comprehensive phylogenetic analysis of the ribonucleotide reductase family reveals an ancestral clade

  1. Audrey A Burnim
  2. Matthew A Spence
  3. Da Xu
  4. Colin J Jackson  Is a corresponding author
  5. Nozomi Ando  Is a corresponding author
  1. Cornell University, United States
  2. Australian National University, Australia
https://doi.org/10.7554/eLife.79790
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  1. Audrey A Burnim
  2. Matthew A Spence
  3. Da Xu
  4. Colin J Jackson
  5. Nozomi Ando
(2022)
Comprehensive phylogenetic analysis of the ribonucleotide reductase family reveals an ancestral clade
eLife 11:e79790.
https://doi.org/10.7554/eLife.79790
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Abstract

Ribonucleotide reductases (RNRs) are used by all free-living organisms and many viruses to catalyze an essential step in the de novo biosynthesis of DNA precursors. RNRs are remarkably diverse by primary sequence and cofactor requirement, while sharing a conserved fold and radical-based mechanism for nucleotide reduction. Here, we structurally aligned the diverse RNR family by the conserved catalytic barrel to reconstruct the first large-scale phylogeny consisting of 6,779 sequences that unites all extant classes of the RNR family and performed evo-velocity analysis to independently validate our evolutionary model. With a robust phylogeny in-hand, we uncovered a novel, phylogenetically distinct clade that is placed as ancestral to the classes I and II RNRs, which we have termed clade Ø. We employed small-angle X-ray scattering (SAXS), cryogenic-electron microscopy (cryo-EM), and AlphaFold2 to investigate a member of this clade from Synechococcus phage S-CBP4 and report the most minimal RNR architecture to-date. Based on our analyses, we propose an evolutionary model of diversification in the RNR family and delineate how our phylogeny can be used as a roadmap for targeted future study.

Data availability

The cryo-EM map has been deposited in the Electron Microscopy Data Bank under accession code EMD-26712, and the model has been deposited in the Protein Data Bank under accession code 7urg. The phylogeny shown in Figure 2 is available at (https://itol.embl.de/shared/yFvz6aVgum9z). The structure-guided sequence alignment and all twenty inferred phylogenies are available for download as supplementary materials.

The following data sets were generated

Article and author information

Author details

  1. Audrey A Burnim

    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9962-1397

  2. Matthew A Spence

    Research School of Chemistry, Australian National University, Canberra, Australia
    Competing interests
    The authors declare that no competing interests exist.

  3. Da Xu

    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Colin J Jackson

    Research School of Chemistry, Australian National University, Canberra, Australia
    For correspondence
    colin.jackson@anu.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6150-3822

  5. Nozomi Ando

    Department of Chemistry and Chemical Biology, Cornell University, Ithaca, United States
    For correspondence
    nozomi.ando@cornell.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7062-1644

Funding

National Science Foundation (MCB-1942668)

  • Nozomi Ando

SAXS was conducted at the Center for High Energy X-ray Sciences (CHEXS), which is supported by the National Science Foundation (NSF) under award DMR-1829070, and the Macromolecular Diffraction at CHESS (MacCHESS) facility, which is supported by award 1-P30-GM124166-01A1 from the National Institute of General Medical Sciences (NIGMS), National Institutes of Health (NIH), and by New York States Empire State Development Corporation (NYSTAR). Cryo-EM work was done using the Cornell Center for Materials Research (CCMR) Shared Facilities

Reviewing Editor

  1. Nir Ben-Tal, Tel Aviv University, Israel

Version history

  1. Preprint posted: April 23, 2022 (view preprint)
  2. Received: April 26, 2022
  3. Accepted: August 31, 2022
  4. Accepted Manuscript published: September 1, 2022 (version 1)
  5. Version of Record published: October 4, 2022 (version 2)

Copyright

© 2022, Burnim et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Audrey A Burnim
  2. Matthew A Spence
  3. Da Xu
  4. Colin J Jackson
  5. Nozomi Ando
(2022)
Comprehensive phylogenetic analysis of the ribonucleotide reductase family reveals an ancestral clade
eLife 11:e79790.
https://doi.org/10.7554/eLife.79790

Share this article

https://doi.org/10.7554/eLife.79790

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