Weirdly Unweird: A Better End to the #Arseniclife Affair

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It’s getting close to two years now since a NASA-funded team of scientists announced they had found a form of life that broke all the rules by using arsenic to build its DNA. It’s become something of an obsession for me. If you want to follow the saga, click here and start back at the earliest post. In July I live-blogged the announcement that other scientists had replicated the experiment and failed to find the same results. In some ways, that was the logical end to the story

My fascination with this story has been tempered from the start by a creepy feeling. As a science writer, I most enjoy reporting on advances in biology: the research that opens up the natural world a little bit wider to our minds. The “#arseniclife” affair was less about biology than about how science gets done and the ways it goes wrong: the serious questions it raised about peer review, replication, and science communication. That fierce debate did some collateral damage. The microbe in question, known as GFAJ-1, went from being the species that would force us to rewrite the biology textbooks to yet another bacterium that offered no serious challenge to the uniformity of life. It became boring.

But biology is not boring. Elephants and redwoods may both be made of the same elements, may both build genes from DNA, may both use the same genetic code book to build proteins–but they’re very different from each other in some respects, and, each in their own way, are most certainly not boring. Neither is GFAJ-1. And so it’s a pleasure to see a new paper in the latest issue of Nature in which a group of scientists pick apart the biology of the microbe and discover something very interesting.

The whole search for arsenic life got its start because arsenic, despite being toxic, is very similar to an essential element, phosphorus. Phosphorus is part of the backbone of DNA, for example, and it is an ingredient in the energy-storing molecule ATP–in each case in a form known as phosphate, with four oxygen atoms tacked on. Arsenate (arsenic linked to three oxygen atoms) is just about identical in size, has a similar charge to its oxygen atoms, and has many other chemical similarities to phosphate.

So the arsenic life team wondered if life might be able to survive with arsenic instead of phosphorus. One way to test that idea would be to rocket off to a planet where there is only arsenic and no phosphorus and look for life. Another would be to look for life on Earth that can swap arsenic for phosphorus. The arsenic life team opted for the latter and headed to Mono Lake in California, the waters of which are loaded with arsenic. They brought a strain of bacteria back to their lab, weaned it off of phosphorus, and supplied it with arsenic instead. The bacteria still grew. That fact and other studies they conducted convinced them that the bacteria had, indeed, become arsenic life.

The consensus today is that the scientists unwittingly fed the bacteria just enough phosphorus to survive, and the tests that seemed to indicate the arsenic was inside the DNA weren’t executed carefully enough.

But think about that for a moment. Imagine what it’s like for a microbe in Mono Lake, or in the lab of a particularly sadistic scientist. You’re drowning in arsenate, and in order to stay alive, to keep growing, you need to grab the precious few phosphate molecules drifting by.

Dan Tawfik, an expert on protein function at the Weizmann Institute in Israel, and his colleagues have uncovered some of GFAJ-1’s secrets to survival.  GFAJ-1 and other bacteria absorb phosphate through their outer membrane, into a sandwiched layer of fluid called the periplasm. Once there, the phosphate is grabbed by so-called phosphate binding proteins, which then deliver the phosphate to the interior of the microbe. Tawfik and his colleagues examined these proteins in unprecedented detail to see how they work.

The scientists offered the proteins a mixture of arsenate and phosphorus. Even when they raised the ratio to 500 molecules of arsenate to every phosphate molecule, the proteins still managed to pluck out phosphate over half the time. The scientists then examined the proteins to figure out how they make such fine discriminations. When the proteins encounter a molecule of phosphate, they enfold it in a tight pocket, which ties down the phosphate with 12 different hydrogen bonds. When arsenate falls into that pocket, it doesn’t quite fit in, and the bond between one of the oxygen atoms in the arsenate and one of the hydrogen atoms in the protein gets twisted. It gets pushed to such an uncomfortable angle that the arsenate drops out.

This finding suggests that ordinary microbes are well-adapted to picking out phosphates when they’re scarce, using their fussy phosphate binding proteins to reject abundant arsenate. GFAJ-1 is stuck in a place where phosphate is always scarce and arsenate is always dangerously copious. Tawfik and his colleagues found that one form of their phosphate binding proteins is spectacularly fussy, preferring phosphates by a factor of 4,500. What’s more, GFAJ-1 produces many copies of this super-fussy protein. As a result, GFAJ-1 can thrive in Mono Lake. In fact, it can handle arsenate-to-phosphate ratios up to 3,000 times higher than found in the lake.

Finding alien life on Earth would have been grand. But seeing how life as we know it manages to adapt to our planet’s extremes is also a pleasure. And it’s a good place for the story of arsenic life to stop: at the point where new science begins.

[Update: Rosie Redfield, the University of British Columbia microbiologist who became a leading skeptic of arsenic life, Maneesh points out in the comments that phosphates are actually abundant in Mono Lake. Thanks for pointing that out, Rosie Maneesh!]

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