Evolution. Tracing oxygen's imprint on earth's metabolic evolution.

L ife on Earth created, and is dependent on, nonequilibrium cycles of electron transfers involving primarily five elements: hydrogen, carbon, nitrogen, oxygen, and sulfur (1). Although biophysical and biochemical reactions catalyze specific electron transfers at a local, molecular level, the metabolic consequences are global. Through opportunity and selection, metabolic pathways evolved to form an interdependent, planetary “electron market” where reductants and oxidants are traded across the globe. The exchanges are made on a planetary scale because gases, produced by all organisms, can be transported around Earth’s surface by the ocean and atmosphere. Exactly how these five elements came to form an electron market place remains largely unresolved, however. On page 1764 of this issue, Raymond and Segrè (2) use an ingenious bioinformatics approach to reveal the evolution of metabolic pathways. Their analysis elegantly reveals not only the profound role that molecular oxygen (O 2 ) has played in shaping the electron market place, but also the evolutionary constraints on, and trajectories of, the ensemble of electron traders. Before the evolution of free O 2 ~2.3 billion years ago (3, 4), there was a glut of reducing equivalents on Earth’s surface. The first traders consumed electrons from the large populations of potential donors, including H 2 , H 2 S, and CH 4 (5). These electrons, extracted either with the release of energy or with the aid of low-energy (infrared) solar photons, were sold at relatively low energy prices to acceptors such as CO 2 and, to a lesser extent, SO 4 . Although there was a very large pool of an alternative electron acceptor, N 2 , considerable metabolic energy is required to reduce the gas to NH 3 at physiological temperatures. Over the first 2 billion years of Earth’s history, the electron market evolved to produce a well-structured set of metabolic pathways distributed among groups of interconnected anaerobic microbes, each selected to conduct one, or at most a small subset, of redox reactions. Because of the relatively large investment in energy to oxidize water, the biggest electron-donor pool, H 2 O, remained biologically inaccessible. When and how the first photosynthetic organisms evolved that were capable of oxidizing water to oxygen remains one of the great mysteries in the evolution of life on Earth (6). However, between ~3.2 and 2.4 billion years ago, either through progressive gene duplication events and selection, or by massive lateral transfer of genes, or both (7, 8), an organism emerged that was capable of extracting four electrons from two molecules of water to form free O 2 as a metabolic waste product. This waste product proved not only highly useful as an electron acceptor, but also potentially damaging to the intricate metabolic As oxygen built up in Earth’s atmosphere during the Precambrian, organisms evolved more complex biochemical networks. This expansion made feasible oxygen-dependent metabolisms that coopted parts of preexisting anaerobic ones. Tracing Oxygen’s Imprint on Earth’s Metabolic Evolution