The evolutionary origins of peroxynitrite signalling

Area of Science:

• Evolutionary Biology
• Biochemistry
• Molecular Biology

Background:

• Peroxynitrite is a reactive signaling intermediate formed from superoxide and nitric oxide radicals.
• The evolutionary origins of peroxynitrite signaling pathways remain largely unexplored.
• NADPH oxidase 5 (NOX5) and endothelial nitric oxide synthase (eNOS) are key enzymes in superoxide and nitric oxide biosynthesis, respectively.

Purpose of the Study:

• To investigate the evolutionary origins of NOX5 and eNOS, enzymes critical for peroxynitrite formation.
• To determine the ancestral origins of animal NOX5 and eNOS through phylogenetic analysis.
• To assess the relevance of studying peroxynitrite-related enzymes in prokaryotes for understanding human physiology.

Main Methods:

• Multiple sequence alignments of NOX5 and eNOS homologues across diverse life domains.
• Phylogenetic analysis of NOX5 to infer evolutionary relationships.
• Review of existing biochemical studies on prokaryotic NOX5 and eNOS homologues.

Main Results:

• Phylogenetic analysis indicates that NOX5 and eNOS were acquired by animals via horizontal gene transfer from ancestral cyanobacteria to early eukaryotes.
• Homologues of NOX5 and eNOS exist in cyanobacteria, suggesting ancient origins for these enzymatic functions.
• Biochemical data from cyanobacterial homologues are likely applicable to understanding human NOX5 and eNOS.

Conclusions:

• The evolutionary trajectory of NOX5 and eNOS suggests a deep evolutionary history rooted in cyanobacteria.
• Understanding peroxynitrite signaling in humans can be informed by studying its ancient biochemical underpinnings in prokaryotes.
• Horizontal gene transfer played a significant role in the evolution of key signaling enzymes in animals.