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Ancient oxygen. Researchers believe that ancient archaea, similar in shape to this Halobacteria, used aerobic respiration 2.9 billion years ago to produce an active form of the B6 vitamin (crystalline structure, inset).

NASA, inset; Wikimedia Commons

The First Oxygen Users?

None of us would be here today if, billions of years ago, a tiny, single-celled organism hadn't started using oxygen to make a living. Researchers don't know exactly when this happened, or why, but a team of scientists has come closer than ever before to finding out. They've identified the earliest known example of aerobic metabolism, the process of using oxygen as fuel. The discovery may even provide clues as to where the oxygen came from in the first place.

To travel so far back in time, evolutionary bioinformaticist Gustavo Caetano-Anollés of the University of Illinois, Urbana-Champaign, along with colleagues in China and South Korea, did a bit of molecular sleuthing. They scoured published genomes from all groups of organisms-although they didn't include viruses in this study-focusing on pieces of proteins known as domains. These pieces have their own distinguishing shapes that provide clues to the protein's function and can be categorized based on various characteristics. Just like a Victorian house has certain features that set it apart from a Tudor mansion, researchers can tell the difference between different domains based on their shape.

Over time, proteins with multiple domains can switch them in and out like Lego blocks, Caetano-Anollés says. This is problematic because the shuffling can obscure the evolutionary origin of a domain. So his group analyzed only proteins with one domain that encoded one function. The researchers hoped that by limiting their study to domains that were involved in aerobic metabolism, they could trace the history of the process.

The team produced a kind of molecular clock by establishing an evolutionary sequence for single-domain proteins. Caetano-Anollés and his colleagues could then tie that sequence to the geologic timeline. By correlating the appearance of domains integral to events such as the rise of eukaryotes, organisms with membrane-bound cellular structures, they could determine an approximate date for the origin of particular domains. "Molecular clocks aren't perfect," Caetano-Anollés acknowledges. "And sometimes they misbehave. But the [domains] that we sampled that were linked to clear-cut events had good agreement."

The researchers found that the most ancient aerobic process was the production of pyridoxal, or the active form of vitamin B6, they report today in Structure. This reaction appeared about 2.9 billion years ago, along with an oxygen-producing enzyme called manganese catalase. This enzyme detoxifies hydrogen peroxide by breaking it down into water and oxygen. Caetano-Anollés hypothesizes that early organisms got the oxygen they needed to produce vitamin B6 from this breakup of hydrogen peroxide. The authors argue that these ancient organisms would have encountered massive amounts of hydrogen peroxide in their environment due to the bombardment of glacial ice by ultraviolet radiation, which can generate the compound.

"It's a great paper in terms of the evolution of protein [domains]," says Paul Falkowski, an evolutionary biogeochemist at Rutgers University in New Brunswick, New Jersey, who wasn't involved in the study. But Timothy Lyons, a biogeochemist at the University of California, Riverside, is skeptical that high levels of hydrogen peroxide were produced by glaciers. "There is little direct evidence for a hydrogen peroxide spike at this time," he says. Still, he says the study is a compelling effort at pinpointing the evolutionary origin of aerobic metabolism.