Sunday, December 5, 2010

Arsenic-aliens? Arsenated-DNA? or simply Arsenic-Adaptation?

                                                         GFAJ-1 bacteria
Even at the risk of sounding deliriously dreamy, I'd say that the impact of the present discovery is such that humans could well be witnessing the emergence of alternative life-forms on earth.  In fact,  existing (but yet-undiscovered) life-forms could well push us enough to gape at the limits of endurance and stunning adaptations of Life. High-dreaming, Science fiction writers now only have to thank NASA for vindicating their way-off-the-scale 'absurd'-imaginations; which of course now seems inane and possible. What was earlier sci-fi is now routine, what was earlier a 'distant-possibility' is now 'present' and possible.  This report raises the possibility that we could indeed well be staring right in the face of creatures which might not care for Carbon.

In other words, there is a heightened likelihood of life-on-earth that uses elements other than what is normally 'prescribed'. The protagonist of this bizarre scientific-discovery (a bacterium) does exactly that - it substitutes Arsenic (As) for Phosphorus (P) in major bio-molecules to sustain its growth. 
But why the chest-thumps? why the brouhaha? Because, the knowledge of the occurrence of  exchange of major bio-elements raises a brazen possibility which could have profound evolutionary and geochemical significance. In fact, it is the first time in the history of biology that there's been anything found that can swap a major element for another in the basic structure. Ha, SETI just got a shot in the arm!
                                                  Are we talking to 'them' yet?!
Important: please visit the "Critique" section at the end of the post for a more nuanced understanding of some of the pitfalls of the paper, discussed in detail by a trained and practicing microbiologist.

Some background: Life on earth depends largely on six major nutrient elements - Carbon [C], Hydrogen [H], Nitrogen [N], oxygen [O], Sulfur [S], and Phosphorus [P], which make up the bulk of the cellular macromolecules - proteins, lipids and DNA. NO element has ever been shown to replace any of the 6-mentioned elements as core-constituents, efficiently and effectively, Never! This is what makes the discovery very special. It goes on to show just that! 
Having said that, let me also mention that As-loving bacteria have been known for some time, and indeed, a previous study by the same group, also published in 'Science', showed that bacteria  (some species of cyanobacteria and others taken from the same source [Mono-Lake, Calif.]) could effectively photosynthesize by extracting electrons from arsenite by oxidation, in order to help convert CO2 to biomass [source]. Undoubtedly, a rigorous scan of extremophiles in our lava-spewing volcanoes, hot-water springs, oceans etc. might throw up other interesting life forms. Indeed, a recent study in PNAS showed that there were hitherto unknown ultrasmall, nanoscale organisms (500 nm in diameter) residing in extreme conditions in a copper mine sludge that is as acidic as battery acid. They called the organisms ARMAN (archaeal Richmond Mine acidophilic nanoorganisms).

Rationale: 'As' is considered to be a chemical-analog of 'P', as it lies directly below P on the periodic table. There are tremendous physico-chemical similarities between their common salts AsO43- and PO43-, but owing to the relative instability of As-salts which get very easily hydrolyzed, they are not incorporated into biological processes [read metabolism], and are actually poisonous.
The question these guys asked was: Would organisms incorporate AsO43- into their system, if theres just no PO43- around? As it turned out, they actually did! Read on.

The bacterium: Samples of the rod-shaped GFAJ-1 bacteria, belonging to the salt-loving Halomonadaceae family of proteobacteria (identified by 16S rRNA sequence phylogeny), were recovered from the toxic, hypersaline and alkaline waters of Mono Lake, California, where the dissolved arsenic concentrations reached upto 200 μM on average, making it one of the highest natural concentrations of As in the world.
methodology: The investigators used lake sediments as inocula into an aerobic defined artificial medium at pH 9.8 containing 10 mM glucose, vitamins, trace metals but no added PO43- nor any additional complex organic supplements (e.g. yeast extract, peptone) with a regimen of increasing AsO43- additions spanning the range 100 μM to 5mM. Currently this isolate, strain GFAJ-1 is maintained aerobically with 40 mM AsO43-, 10 mM glucose and no added PO43- (+As/-P condition).

Stoichiometry and elemental distribution in the cell: Investigators used radiolabeled [73-AsO4-3-] to obtain more specific information about the intracellular distribution of arsenic. Wolfe-Simon and colleagues learned that about one-tenth of the arsenic absorbed by the bacteria ended up in their nucleic acids, but more than three quarters of the 73-AsO4-3- into the protein fraction, with a small fraction going into lipids.
This meant that the bacteria indeed could use As as a substitute, and was not merely using [and reusing] the scarce P-pool. 
Data produced by mass-spectrometry methods known as ICP-MS and NanoSIMS, showing the distribution of various chemical elements within GFAJ-1 cells, revealed a clear difference between cells grown with As [which were loaded with As] and those grown with P [had very little phosphorus]. In cells grown with phosphorus, the opposite was true. 
To confirm that the As was actually being incorporated into DNA, folks used gel purification of DNA to isolate and concentrate DNA from GFAJ-1 cells.
NanoSIMS measurement of these concentrated DNA extractions showed that arsenic was indeed present in their DNA.
Clinching evidence came from Micro extended X-ray absorption fine structure spectroscopy (µEXAFS) experiments, which showed that As bonded to O and C in the same way P bonds to O.
In other words: GFAJ-1 probably can substitute As for P in its DNA and all the while continue its life happily with children, as if nothing happened!

Now that we revere the DNA molecule as the 'ladder-of-life', and P [phosphate] as the backbone of this fantastic ladder [the basic DNA structure is here]; this study hits at the very-bottom of all dogmas and beliefs, by hinting that there could be alternatives to the elements. It reinforces what SETI-believers and star-wars worshippers have long been ranting about; that life can exist under a much wider range of environments than hitherto believed. GFAJ-1 are proof of life’s amazing ability to adapt to even the most difficult conditions. 
But really, are we looking at Arsenated-DNA yet? Life forms that operate beyond the realms of  the mandatory 6-elements? Maybe [or not]!

Questions that remain:
*Does all the phosphate get replaced by arsenates in the backbone of DNA? Then [by virute of its
  inherent instability], every bond in that chain would hydrolyze in minutes.
*Alternatively, if there is an arsenate-for-Phosphate structure, it has to be seriously stabilized by some as-yet-unknown mechanism. We dont know that yet.
*None of the measurements clearly proves that Arsenate is doing what phosphate normally would, in the DNA [although presently its difficult to come up with an alternative explanation].
*Does GFAJ-1 actively employ its arsenic-incorporating ability in its natural state, in the lake; or is it some very bizarre thing, which happens only under controlled laboratory-conditions.
*And, are there other As-using forms waiting to be discovered? Maybe even forms which have done away with DNA?

*These bacteria might one day help to clean up arsenic-contaminated drinking water 
*Or, clean up and bio-remediation after an oil spill [read the disastrous effects of Oil-spill in an earlier post]. 
*The field of custom-engineering microbes is a hot area of alternative energy. A synthetic organism that works by different chemicals entirely might actually just as important as the new arsenic-eating GFAJ-1 bacterium.
But a point to ponder is that GFeAJ-1 does NOT preferentially use As over P, hence all its usage would have to be limited to P-free environs.

Critique: following links lead to an expert's critique (Dr. Rosemary (Rosie) J. Redfield, a microbiologist at University of British Columbia) of the claims made in the paper, posted in her blog. She's torn the paper apart on issues of microbial-assays, but (admittedly) is not an expert on the biophysical aspects of the paper.

* Here is a very insightful paper [Science, 1987,  Vol. 235, 1173-1178], with valuable references which discuss why Nature chose Phosphates as a fundamental building block [and not Arsenate, Citrate or Silicate].

** A Bacterium That Can Grow by Using Arsenic Instead of Phosphorus [here]
    Felisa Wolfe-Simon1, 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 and Ronald S. Oremland.
    Science, DOI: 10.1126/science.1197258, published Online 2 December 2010.

** "Microbe gets toxic response"

** Arsenic-eating microbe may redefine chemistry of life [Nature news, here]

** Arsenic eating bacteria opens new possibilities for alien life [here]

** Arsenic-based bacteria point to new life forms [here]


  1. Hello friends,

    Interesting. The cell is the fundamental unit of structure and function in living organisms. Thanks a lot......

    Regulatory T Cells

  2. Excellent and very comprehensive article.
    Thank you.