Reconstruction of Nitrogenase Predecessors Suggests Origin from Maturase-Like Proteins

Genome Biol Evol. 2022 Mar 2;14(3):evac031. doi: 10.1093/gbe/evac031.


The evolution of biological nitrogen fixation, uniquely catalyzed by nitrogenase enzymes, has been one of the most consequential biogeochemical innovations over life's history. Though understanding the early evolution of nitrogen fixation has been a longstanding goal from molecular, biogeochemical, and planetary perspectives, its origins remain enigmatic. In this study, we reconstructed the evolutionary histories of nitrogenases, as well as homologous maturase proteins that participate in the assembly of the nitrogenase active-site cofactor but are not able to fix nitrogen. We combined phylogenetic and ancestral sequence inference with an analysis of predicted functionally divergent sites between nitrogenases and maturases to infer the nitrogen-fixing capabilities of their shared ancestors. Our results provide phylogenetic constraints to the emergence of nitrogen fixation and are consistent with a model wherein nitrogenases emerged from maturase-like predecessors. Though the precise functional role of such a predecessor protein remains speculative, our results highlight evolutionary contingency as a significant factor shaping the evolution of a biogeochemically essential enzyme.

Keywords: ancestral sequence reconstruction; early life; historical contingency; maturase; nitrogen fixation; nitrogenase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalytic Domain
  • Nitrogen / metabolism
  • Nitrogen Fixation* / genetics
  • Nitrogenase* / genetics
  • Phylogeny


  • Nitrogenase
  • Nitrogen