All living organisms on this planet use six elements for almost all of the chemical structures of DNA, RNA, proteins, and lipids. There is a smattering of other elements, mostly metals, that are essential for biological functions (e.g., the iron in hemoglobin). However, we wouldn’t expect to find anything outside of carbon, hydrogen, oxygen, nitrogen, sulfur and phosphorus in the basic structures of biomolecules. Surprisingly, a team of scientists provide evidence in Science that another element, arsenic, can be incorporated into the basic chemical makeup of the macromolecules of life, replacing some of its phosphorus.

Evolutionary geochemist Felisa Wolfe-Simon, the lead author, and her colleagues found a strain of bacterium (GFAJ-1 of the Halomonadaceae family) that can grow in a medium abundant in arsenic and lacking phosphorus. The GFAJ-1 bacterium naturally resides in the arsenic-rich waters (200 uM) of Mono Lake located in California's Eastern Sierra, and it belongs to a family of proteobacteria that is known to accumulate arsenic. It's not remarkable that GFAJ-1 survives in high concentrations of arsenic, but what is startling is that it potentially integrates arsenic into its DNA and proteins.

Arsenic is chemically similar to phosphorus, which has a large presence in biomolecules in the form of phosphate (PO 4 3-). That’s partly why arsenic is so toxic. In physiological conditions, phosphate and arsenate (AsO 4 3-) are analogous enough that some metabolic pathways cannot tell them apart initially. But incorporation of arsenic disrupts later steps in these pathways, most likely due to arsenic compounds’ relative instability and lower resistance to hydrolysis.

The researchers propose that, if an organism possesses an ability to overcome arsenate’s instability, it might be able to exchange phosphorus for arsenic in biological pathways. To test their hypothesis, they extracted GFAJ-1 from Mono Lake and subjected the bacteria to an artificial medium with increasing concentrations of arsenate and only trace amounts of phosphate.

GFAJ-1 bacteria grew slower with arsenate than they would with phosphate, but they were still able to increase their cell count by 20-fold in six days. The cells ended up containing 0.19 percent arsenic by dry weight compared to just 0.001 percent in the control cells. More importantly, the cells grown in arsenate were noticeably different in morphology from the control population. They were 1.5 times bigger by volume and developed large vacuole-like regions inside the cells.

Rather than just retaining arsenic inside the cells, the authors provided evidence that the bacteria actually integrated arsenic into DNA and possibly other biomolecules. They found higher arsenic and lower phosphorus content in purified genomic DNA of bacteria grown in arsenate compared to control cells.

Synchrotron X-ray studies of intracellular arsenic revealed that it is mostly likely bound to four oxygen atoms and then distally bound to a carbon atom. This configuration is consistent with arsenic replacing phosphorus in the backbone DNA. Substitution of elements is known to occur in biological processes (e.g., copper in hemocyanin vs. iron in hemoglobin for oxygen transport), but it has not been seen in something as fundamental as the structure of DNA, nor has it been observed with arsenic.

The researchers found evidence that bacteria may also incorporate arsenic into proteins and metabolites. Fractions from cellular extractions corresponding to proteins and metabolites contained significant amounts of arsenic, suggesting that it is chemically integrated. Nonetheless, high resolution analysis of purified products would provide more concrete evidence.

Somehow GFAJ-1 found a way to compensate for the instability of arsenate and use it to alter the chemical makeup of its primary biomolecules. The authors propose that the vacuole-like regions could contain large amounts of poly-β-hydroxybutyrate, which stabilizes arsenic compounds and could assist the assimilation of arsenate.

The researchers’ discovery that bacteria can substitute phosphorus with arsenic in the backbone of DNA has significant implications for evolutionary chemistry and astrobiology, since it suggests that life won't necessarily be limited to the six elements it favors here on Earth. In fact, NASA announced a press conference on these results as relevant to the search for extraterrestrial life, which set off a wave of speculation as to what the agency knew.

Further investigation is necessary to find the exact mechanism of arsenic substitution. Moreover, these research results raise the question of whether or not other elements can stand-in for one of life’s six key elements.

Science, 2010. DOI: 10.1126/science.1197258

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