Ribonucleotide reductases: the evolution of allosteric regulation

Area of Science:

• Biochemistry
• Molecular Biology
• Evolutionary Biology

Background:

• Ribonucleotide reductases (RNRs) are vital enzymes for DNA replication and repair in all organisms.
• Their evolution marked a transition from an RNA world to the DNA-RNA-protein system.
• Three distinct classes of RNRs exist, sharing similar allosteric regulation despite structural differences.

Purpose of the Study:

• To explore the diversity and evolution of the three classes of ribonucleotide reductases.
• To describe the allosteric regulation mechanisms common to all RNR classes.
• To propose an evolutionary model for RNR diversification, linking it to the rise of oxygen.

Main Methods:

• Comparative analysis of the three RNR classes.
• Review of evolutionary evidence.
• Examination of allosteric regulation mechanisms.

Main Results:

• Significant structural diversity exists among the three RNR classes.
• Allosteric regulation of substrate specificity is conserved across classes.
• The emergence of oxygen likely drove RNR diversification.

Conclusions:

• Class III anaerobic RNRs, utilizing iron-sulfur clusters and S-adenosylmethionine, are the most likely ancestors.
• Understanding RNR evolution provides insights into early life biochemistry.
• Enzyme evolution is intrinsically linked to environmental changes, such as oxygenation.