Evolutionary and comparative aspects of nitric oxide, carbon monoxide and hydrogen sulfide

Respir Physiol Neurobiol. 2012 Nov 15;184(2):117-29. doi: 10.1016/j.resp.2012.04.004. Epub 2012 Apr 20.


The concept that non-respiratory gases, such as nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H(2)S) functioned as signaling moieties is a relatively recent development, due in part to their ephemeral existence in biological tissues. However, from an evolutionary perspective these gases dominated the prebiotic and anoxic Earth and were major contributors to the origin of life and the advent of eukaryotic animals. As Earth's oxygen levels rose, NO, CO and H(2)S disappeared from the environment and cells began to utilize their now well-developed metabolic pathways to compartmentalize and regulate these three gases for signaling purposes. Ironically, many of the signaling pathways have become now intimately involved in regulating oxygen delivery and their evolution has continued well into the vertebrates. This review examines the role NO, CO and H(2)S played in early life and their regulatory roles in oxygen delivery during the course of vertebrate evolution.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Biological Evolution*
  • Carbon Monoxide / metabolism
  • Carbon Monoxide / physiology*
  • Humans
  • Hydrogen Sulfide* / metabolism
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / physiology*
  • Respiratory Physiological Phenomena
  • Signal Transduction / physiology


  • Nitric Oxide
  • Carbon Monoxide
  • Hydrogen Sulfide