Unmasking the ancestral activity of integron integrases reveals a smooth evolutionary transition during functional innovation

Nat Commun. 2016 Mar 10;7:10937. doi: 10.1038/ncomms10937.

Abstract

Tyrosine (Y)-recombinases have evolved to deliver mechanistically different reactions on a variety of substrates, but these evolutionary transitions are poorly understood. Among them, integron integrases are hybrid systems recombining single- and double-stranded DNA partners. These reactions are asymmetric and need a replicative resolution pathway, an exception to the canonical second strand exchange model of Y-recombinases. Integron integrases possess a specific domain for this specialized pathway. Here we show that despite this, integrases are still capable of efficiently operating the ancestral second strand exchange in symmetrical reactions between double-stranded substrates. During these reactions, both strands are reactive and Holliday junction resolution can follow either pathway. A novel deep-sequencing approach allows mapping of the crossover point for the second strand exchange. The persistence of the ancestral activity in integrases illustrates their robustness and shows that innovation towards new recombination substrates and resolution pathways was a smooth evolutionary process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Bacteriophage lambda / genetics*
  • Computer Simulation
  • DNA / metabolism*
  • DNA, Cruciform
  • DNA, Single-Stranded / metabolism*
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / genetics*
  • Evolution, Molecular
  • In Vitro Techniques
  • Integrases / genetics*
  • Integrons / genetics*
  • Nucleic Acid Conformation
  • Protein Structure, Tertiary
  • Vibrio cholerae / genetics
  • Vibrio cholerae / metabolism

Substances

  • Bacterial Proteins
  • DNA, Cruciform
  • DNA, Single-Stranded
  • Escherichia coli Proteins
  • DNA
  • Integrases