When cooking up the stuff of life, you can’t just substitute margarine for butter. Or so scientists thought.

But now researchers have coaxed a microbe to build itself with arsenic in the place of phosphorus, an unprecedented substitution of one of the six essential ingredients of life. The bacterium appears to have incorporated a form of arsenic into its cellular machinery, and even its DNA, scientists report online Dec. 2 in Science.

Arsenic is toxic and is thought to be too chemically unstable to do the work of phosphorus, which includes tasks such as holding DNA in a tidy double helix, activating proteins and getting passed around to provide energy in cells. If the new results are validated, they have huge implications for basic biochemistry and the origin and evolution of life, both on Earth and elsewhere in the universe.

“This is an amazing result, a striking, very important and astonishing result – if true,” says molecular chemist Alan Schwartz of Radboud University Nijmegen in the Netherlands. “I’m even more skeptical than usual, because of the implications. But it is fascinating work. It is original, and it is possibly very important.”

The experiments began with sediment from eastern California’s Mono Lake, which teems with shrimp, flies and algae that can survive the lake’s strange chemistry. Mono Lake formed in a closed basin — any water that leaves does so by evaporation – making the lake almost three times as salty as the ocean. It is highly alkaline and rich in carbonates, phosphorus, arsenic and sulfur.

Led by Felisa Wolfe-Simon of NASA’s Astrobiology Institute and the U.S. Geological Survey in Menlo Park, California, the researchers cultured microbes from the Lake Mono sediment. The microbes got a typical diet of sugar, vitamins and some trace metals, but no phosphate, biology’s favorite form of phosphorus. Then the team started force-feeding the critters arsenate, an analogous form of arsenic, in greater and greater quantities.

One microbe in particular – now identified as strain GFAJ-1 of the salt-loving, mostly marine family Halomonadaceae – was plucked out and cultured in test tubes. Some were fed loads of arsenate; others got phosphate. While the microbes subsisting on arsenate didn’t grow as much as those getting phosphate, they still grew steadily, doubling their ranks every two days, says Wolfe-Simon. And while the research team couldn’t eliminate every trace of the phosphate from the original culture, detection and analytical techniques suggests that GFAJ-1 started using arsenate as a building block in phosphate’s place.

“These data show that we are getting substitution across the board,” Wolfe-Simon says. “This microbe, if we are correct, has solved the challenge of being alive in a different way.”

Arsenic sits right below phosphorus in the periodic table and so, chemically speaking, isn’t that different, Wolfe-Simon notes. And of the six essential elements of life – carbon, hydrogen, nitrogen, oxygen, phosphorus and sulfur (aka CHNOPS) – phosphorus has a relatively spotty distribution on the Earth’s surface. If a microbe in a test tube can be coerced to live on arsenic, perhaps life’s primordial home was also arsenic-rich and life that used phosphorus came later. A “shadow biosphere” of arsenic-based life may even exist unseen on Earth, or on some lonely rock in space.

“It isn’t about arsenic, and it isn’t about Mono Lake,” says Wolfe-Simon. “There’s something fundamental about understanding the flexibility of life. Any life, a microbe, a tree, you grind it up and it’s going to be CHNOPS. But we have a single sample of life. You can’t look for what you don’t know.”

Similarities between arsenic and phosphorus are also what make the element so poisonous. Life often can’t distinguish between the two, and arsenic can insinuate itself into cells. There, it competes with phosphorus, grabs onto sulfur groups, or otherwise gums up the works, causing cell death. Some microbes “breathe” by passing electrons to arsenic, but even in those cases the toxic element stays outside the cell.

Researchers are having a hard time wrapping their minds around arsenate doing the job of phosphate in cells. The ‘P’ in ATP, the energy currency for all of life, stands for phosphate. And the backbone of the DNA double helix, the molecule containing the genetic instructions for life, is made of phosphate. Basic biochemistry says that these molecules would be so unstable that they would fall apart if they were built with arsenate instead of phosphate.

“Every organism that we know of uses ATP and phosphorylated DNA,” says biogeochemist Matthew Pasek of the University of South Florida in Tampa. He says the new research is both fascinating and fantastic. So fantastic, that a lot of work is needed to conclusively show exactly how the microbe is using arsenate.

Both phosphate and arsenate can clump up into groups, and with their slightly negative electric charge, slightly positive DNA would be attracted to such clumps, says Pasek. Perhaps the arsenic detected in the DNA fraction was actually a nearby clump that the DNA wrapped itself around, he speculates.

The microbe may be substituting for phosphate with discretion, says geochemist Everett Shock of Arizona State University in Tempe, using arsenic in some places but not others. But Shock says the real value of the work isn’t in the specifics. “This introduces the possibility that there can be a substitution for one of the major elements of life,” he says. Such research "stretches the perspective. Now we’ll have to see how far this can go."

Images: Science/AAAS

See Also: