A new life form? Not so fast

So everybody is excited about the new GFAJ-1 bacterium that Felisa Wolfe-Simon and her colleagues have discovered. A common buzzphrase diffusing through the media and blogosphere is “NASA discovers a new  life form“. (Or, better yet alien life.) Big press conference, and I just finished going through  the article that Wolfe-Simon and colleagues have published in Science. Great work. But is this really a new life form?

Alien life on Earth. Credit: popculturegeek.com

Recap: A few years ago Wolfe-Simon and colleagues discovered that arsenic can be used as an electron donor and acceptor in certain bacteria which live in arsenic-rich conditions.  That was really cool and interesting, because arsenic, usually a poison, is used by these bacteria to breathe, one of the most basic functions of life.

About Arsenic

The “poison of the aristocrats” is toxic to most life simply because arsenic resembles very closely one of the most basic atoms of life:  phosphorus. Phosphorus is used in the cell membrane, in proteins, as a signalling molecule, as part of the energy “coinage” (ATP), and in the DNA backbone. Ingesting arsenic fools life’s machinery into thinking that it is actually phosphorus and incorporate it. But that’s when the machinery starts breaking down, because arsenic is not phosphorous, and it gums up the works. It’s like putting cooking oil on your car instead of motor oil. Your car may run for a while, but pretty soon smoking and seizing will start, and your engine will die.

Martha Wise poisoned her mother, Sophia, Hazel, and her uncle and aunt; Fred; Glenke, Sr., and wife. Credit: the PK paper, Flickr

But GFAJ-1 seems to be using arsenic as a replacement for phosphorous. Actually, it manages to grow in media that  only has trace amounts of phosphate, and large concentrations of arsenate. (The “-ate” suffixsimply means the oxygenated form of both elements: PO3 for phosphate and AsO4 for arsenate.) GFAJ-1 goes forth and multiplies in arsenate-only conditions, but not in media that are devoid of  arsenate and phosphate. It actually grows best with phosphate. So the growth rates induced by the nutrients looks like this: phosphate > arsenate > nothing. When growing GFAJ-1on arsenate, the scientists also measured the intracellular concentration of phosphate, and it was well below what was needed to sustain life.  Does that mean GFAJ-1 uses arsenate instead of phosphate? To answer this question, the scientists used radiolabeled arsenate to answer that question. The radioactive arsenate was detected mostly in the DNA, also in proteins, but some was also found in the membrane. Also, the arsenate-growing bacteria had much less phosphate in them than is necessary to sustain life.

So it seems that arsenate is being used by the cells in lieu of phosphate, but is arsenate truly being incorporated into biomolecules in the same manner as phosphate? The researchers checked that with DNA, looking at the structure using synchrotron X-ray studies. This technique let them look at the actual structure of the DNA, although the resolution is not as good as that of X-ray crystallography. They did find that arsenate was incorporated in the DNA backbone in the same manner of phosphate.

And not only does GFAJ-1 survive, it thrives. A  Following such a radical change from known biochemistry. Since the arsenate is in the DNA,  it means that the whole DNA-replication and transcription machinery — hundreds of proteins — are all adapted to replicating and transcribing arsenate DNA (and very likely arsenate RNA too!)

Does all this mean GFAJ-1 is a new form of life?

New Life?

The current thought is that all life on earth is descended from LUCA: the Last Universal Common Ancestor. LUCA had several traits that were incorporated into all life, such as lipid membranes, DNA as the genetic material, proteins as cellular machinery and also using phosphorous in several critical roles in life, including in the DNA backbone. So “new life” would mean that GFA-J1 is derived from a different common ancestor. If this is the case, than GFA-J1 is indeed a new life form, and the implications of this finding are mind-boggling: why stop at two ancestors? Why not three, five, or 1,000 different ancestors to life on earth, each producing its own biochemical progeny, with its own unique traits? After all, the reason we may not recognize biochemically-distinct life as life, is that we are not looking for it. All our tools are geared to detecting and analyzing life with the biochemistry we know. The fact that this team of scientists have managed to use tools to analyze such a deviation from known biochemistry is a huge accomplishment. Just look how long it took us to find this radical, yet oddly familiar, departure from conventional phosphate-based biochemistry.

ResearchBlogging.org

The question therefore is now: does substituting phosphorous by arsenic in the backbone mean that GFAJ-1 is derived from a different common ancestor than all other life that we know on earth? Unlikely. I would say that using arsenic as a phosphorus substitute is a very radical adaptation to phosphorus poor and arsenic-rich conditions. GFAJ-1 is still using the same biochemistry, with a heavy phosphorus adaptation. Obviously, many enzymes are adjusted to the arsenate lifestyle. Sequencing GFAJ-1′s genome would probably be the next step, as this could provide us with leads as to how enzymes in GFAJ-1  can use arsenate and arsenate containing molecules.

In brief: bacteria  uses arsenic instead of phsophorus. Cool and exciting? Definitely. Is this huge? Yes. Extends our biochemical horizons? Certainly. New life? Unlikely


Felisa Wolfe-Simon, Jodi Switzer Blum, Thomas R. Kulp, Gwyneth W. Gordon, Shelley E. Hoeft, Jennifer Pett-Ridge, John F. Stolz, Samuel M. Webb, Peter K. Weber, Paul C. W. Davies, Ariel D. Anbar, & Ronald S. Oremland (2010). A Bacterium That Can Grow by Using Arsenic Instead of Phosphorus Science : 10.1126/science.1197258

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8 Responses to “A new life form? Not so fast”

  1. edgeArchitect says:

    And how about the fact that the Lifeform is from another planet?
    Does this not surprise anyone? Are we too used to seeing Aliens?
    What are the implications for religions?

    I think all of these things have to be considered when judging the impact the discovery might have on our daily lives and new directions which science may take towards making more discoveries.

  2. Hi BSB, when you discuss the -ate suffix, you accidentally wrote PO3, instead of PO4. [PO3]2- is phosphite, not phosphate. Phosphate is [PO4]2-. Then the (bio)chemical analogy with arsenate is clear too.

  3. @Egon Willighagen

    Hahaha… and of course, the charge on those -ates is -3, not -2 :(

  4. intercostal says:

    >>And how about the fact that the Lifeform is from another planet?

    It doesn’t seem to be.

    >>What are the implications for religions?

    None. Even if it WERE alien, I don’t see why a newly discovered microorganism on another planet would have any more religious implications than a newly discovered microorganism on Earth.

    The religious implications only really arise if we discovered another species capable of asking the Big Questions; that’s a big jump from a bacterium. Then we’d be seeing big questions about human uniqueness, the application of human rights to non-human sapients, souls of aliens, etc.

  5. Dan Gaston says:

    The New Life bit isn’t event unlikely, I think it is pretty clear that GFAJ-1 groups pretty solidly within existing bacteria phylogenetically. It belongs to the Halomonadaceae, which fall within the Proteobacteria. It is a secondary adaptation to high arsenic conditions.

  6. The recent announcement by NASA scientists and their collaborators that the GFAJ-1 strain of the Halomonadaceae bacteria provides hints into the potential biology of alien life-forms and the response of the media and scientific community to this claim have revealed several disturbing trends. These include the desperation of a government-funded science agency to generate publicity at a time when its financial support is in jeopardy; the inadequacy of the experiments by these researchers to support their conclusions; the relatively poor peer-review by one of the most prestigious of scientific journals; and the extra-hype added by the mass media. One rather positive aspect of this affair is the rapid response of the scientific community to question and challenge the most poorly supported and far reaching claims. It is likely that they will be disregarded much faster than the previous announcement by NASA of petrified Martian life in an Antarctic meteorite.

    A few of my colleagues as well as numerous bloggers have noted that the NASA publicity machine has been coincidently cranked up at a time when the next US budget, including the funding for NASA, is under question. The discovery of the model organism described in the Wolfe-Simon et al. paper in Science is actually not new. Since the mid-nineties, the ongoing study of various strains of Halomonadaceae bacteria and their respiration of arsenic at Mono Lake, the Aberjona Watershed and elsewhere has been reported by Dr. Ronald Oremland (the senior author of the Wolfe-Simon et al. paper) and independently by others.

    The central claim of the new Wolfe-Simon et al. study is that arsenic can substitute for phosphorus to sustain the growth of the GFAJ-1 bacterial strain, and some evidence is offered that the arsenic is incorporated into macromolecules such as nucleic acids and proteins. The GFAJ-1 cells were cultivated in the near absence of phosphorus in the growth media in the presence of arsenic. However, the media used in the study apparently had about 3 µM phosphorus, and one wonders whether phosphorus may have also been introduced with the culture plates that may have been pre-washed with phosphate-containing detergents. In any event, the cultured GFAJ-1 cells were still observed to contain phosphorus at about 1% of the levels seen in cells grown in the presence of high phosphorus. Even under these conditions, bathing in medium containing arsenic, these cells still featured 100-times more phosphorus than arsenic. Moreover, the levels of arsenic incorporated into the phosphorus-depleted bacteria was not that much different from phosphorus-supplemented GFAJ-1 cells grown without arsenic. Ideally, a synchrotron X-ray analysis of arsenic in biomolecules should have been undertaken for both the phosphorus-fed and starved populations of the bacteria rather than just the phosphorus-depleted cells as was performed in the study.

    Despite the speculations offered in the Wolfe-Simon et al. paper, no conclusive evidence was provided that any arsenic actually replaced phosphorus in the DNA backbone of the GFAJ-1 cells. To incorporate arsenic into nucleotides and proteins, the arsenic would have to be presented with the arsenic-containing equivalent of adenosine tri-phosphate (ATP), i.e. adenosine tri-arsenate (ATAs). No evidence was obtained for the presence of ATAs in the GFAJ-1 bacteria. In fact, I have been unable to find any reports of ATAs in any life-form from PubMed or Google searches.

    While arsenic and phosphorus are highly related in the periodic table of elements, the arsenic atom is slightly more than double the molecular mass of phosphorus. As atoms get larger, the electronic structure of the atom, particularly those parts that participate in chemical bonds, become increasingly diffuse. Consequently, arsenate esters are very unstable and hydrolyze markedly faster than phosphate esters. This instability of arsenate ester linkages really restricts their utility in the synthesis of macromolecules like DNA. Furthermore, the instability of arsenylation of proteins, would precludes it from effectively replacing protein phosphorylation. Protein phosphorylation appears to be the major post-translational regulatory mechanism for the emergence of eukaryotic organisms and seems to be required for the development of multi-cellular organisms.

    While the existence of stable ATAs is doubtful, it is more feasible that adenosine-diphosphate, mono-arsenate (ADPAs) might be produced that could fuel arsenylation reactions. Even if ADPAs exists, it is still difficult to reconcile the use of arsenate by a wide range of enzymes to replace all of the diverse metabolic and structural roles (e.g. nucleic acids, phospholipids, phosphoproteins) of phosphate in even bacteria. It is unlikely ADPAs would have a stable enough high energy bond between the gamma arsenic and oxygen atoms to serve as an efficient source of chemical energy. ATP is optimal in all biological systems on this planet with an intermediary position between the higher energy compounds from which ATP accepts phosphate and the lower-energy compounds from which it donates phosphate. Consequently, an organism that exclusively utilizes arsenic and not phosphorus would have a profoundly different metabolism with very different metabolites and macromolecules.

    As a member of the wide-spread Gammaproteobacteria, the Halomondadaceae bacteria clearly do not represent an alternatively evolved family of life-forms, but are well adapted to endure extreme conditions. These organisms are also commonly dispersed in environments in which “normal” microbes proliferate, which is most probably where they originated. The GFAJ-1 bacteria actually prospered better in the presence of phosphorus. Those grown in the presence of arsenic and near absence of phosphorus became bloated in size by approximately 60%. This was due to the appearance of large “empty” vacuoles in the bacteria. It seems that this organism functions optimally in phosphorus, but tolerates arsenic. This is not surprising, since the concentration of phosphorus in the Earth’s crust is around 1000 parts per million (ppm), which is about 500-times higher than measured for arsenic. Such a relative distribution of these two elements is likely to be universal, as more energy is required to forge arsenic atoms than phosphorus atoms.

    Many metals can poorly mimic each other as cofactors in enzyme-catalyzed reactions. This is why a few are highly toxic such as lead and mercury. The fidelity of enzymes for their optimal elements is not 100%, so it is not surprising if trace arsenic can replace phosphorus in the structures of small molecules and macromolecules. Many marine organisms, including clams and sea weeds can also accumulate arsenic. This is likely to be a protective response to reduce the threat of predation by animals that might try to consume them. Arsenic is particularly toxic in eukaryotic organisms, because amongst other many other problems, arsenic inhibits pyruvate dehydrogenase in the citric acid cycle and it uncouples oxidative phosphorylation in the mitochondria, both of which inhibit ATP synthesis. It seems probable that the Halomonadaceae bacteria have acquired the ability to tolerate arsenic, most likely to avoid being eaten. They may concentrate arsenic-containing compounds in vacuoles for this purpose, and they are known to excrete arsenic, presumably when it becomes too toxic for the bacteria themselves. This ability provides the opportunity for these bacteria to thrive in arsenic-rich environments where most other bacteria cannot.

    The lessons from all of this hype from a US government agency, a peer-reviewed scientific journal, and the popular press will likely go unheeded. Unfortunately, too many research institutions that depend on public funding through government agencies and charity will continue to feel pressured to over blow their latest scientific breakthroughs to justify the massive amounts of financial support that they have received. However, with the increasing ability of the wider scientific community to rapidly challenge these assertions in the Internet age, they do so at the peril of their credibility.

  7. Iddo says:

    Well, seems like the whole story, upon deeper investigation, is yet unproven. See Rosie Redfield (and others’) dissection. I expect we will see some interesting correspondence in next week’s Science.

  8. Iddo says:

    @S. Pelech – Kinexus
    Thanks for putting such a well-considered comment. :)