Arsenic and old DNA

Arsenic, the infamous "inheritance powder" has been the villain in many an Agatha Christie mystery.  Cary Grant was at his endearing best in the black comedy "Arsenic and Old Lace".  There has been hue and cry over arsenic pollution of waterways in the past decade.  Ground water contamination with arsenic has caused much loss in developing countries such as Bangladesh and India. 

Arsenic has come into the limelight again. This time not as a toxin, but as proof of concept for alternate life in a shadow biosphere.

A recent possibly groundbreaking paper reports the incorporation of Arsenic in the DNA of a bacterium.  Felisa Wolfe-Simon and her team of specialists from various research labs in the US have reportedly grown a strain of bacteria, GFAJ-1, isolated from Mono Lake bottom sediment, under carefully controlled conditions with arsenic in its building block. 

The Team

Arsenic contamination of water is a serious concern because of its high toxicity to man and other animals.  The toxicity of arsenic stems from its reaction with lipoic acid, an important constituent of many enzymes. Acetyl CoA, a co-enzyme that plays a critical role in the biochemical pathyway to metabolism, called the citric acid cycle or the Krebbs cycle, is derived from lipoic acid - see an animation on the role of lipoic acid on acetyl CoA synthesis here.  Arsenic binds with the two sulfur groups of dihydrolipoic acid [Figure below], thereby preventing formation of Acetyl CoA, and in effect completely stopping metabolism. Arsenic can disrupt other biochemical pathways as well, leading to a variety of maladies, ranging from mild dermatological lesions to, in extreme cases, multi-organ failure and death.

Arsenic bonding wtih lipoic acid

Almost a decade back, scientists discovered bacteria in the polluted Aberjona Watershed in Massachusetts, that were known to survive high arsenic environments.  Subsequent studies have shown that arsenic resistance has been imparted to these micro organisms in many ways.   Some bacteria and fungi convert arsenate into gaseous species of arsenic (“arsine”, as corny as that may sound), which by itself is highly toxic to humans but the bacteria can thus get rid of the arsenic inside them.  Some marine algae are known to convert arsenic compounds into fat-soluble substances that can be excreted from their body. Yet a few have developed strategies to include arsenic into their metabolic cycle, so that instead of killing them, arsenic actually fuels their living. 

Arsenic comes right below phosphorous in the periodic table, and hence is very similar to phosphorous in its chemistry.  Ideally, it can replace phosphorous in many biochemicals, such as proteins and lipids.  Even DNA, the building block of life as we know it, has phosphorous in it [figure below], which could potentially be replaced by arsenic.  However, arsenic compounds, especially Arsenic-carbon bonds are very unstable, and given a choice, the carbon would preferentially bond with phosphorous than arsenic.  The affinity for protienaceous carbon to phosphorous is four times as much as that with arsenic, making it difficult to find arsenic based life forms on earth.  Despite evidence of life forms that thrive in arsenic rich environments, there has been no prior proof on the incorporation of arsenic inside the life-power – the DNA.

Phosphorous in DNA [Adapted from here]

What if the bacteria were NOT given the choice?  That is what Felisa and coworkers did.  The bacterium characterized by its resistance to arsenic was fed on an exclusive arsenic diet, completely free of all sources of phosphorous. The arsenic feed was radioactively labeled to track its presence in the cells.  A high risk experiment, because the chance of survival in such strenuous environment is bleak. Yet, some survived. When the bacteria were analyzed by chemical and biochemical analytical techniques, the arsenic was found to be incorporated into intracellular chemicals, not merely as impurities but as ingredients.  When DNA was isolated and analyzed, they were found to contain arsenic.

But arsenic-carbon bonds are unstable.  So, what stabilizes the arsenical DNA here?  The arsenate ester bonds are particularly unstable in aqueous environment. And the cell is 70-90% water. The researchers explain that they also found vacuoles in the cells with poly-b-hydroxy butrate, a hydrophobic material, which probably gives the arsenic-ester bonds more chance to survive by its water repellent properties.

Arsenic-grown bacterial cells with vacuoles containing hydrophobic poly-b-hydroxy butrate [Source: Original paper]

As with any new discovery/idea/conjecture, this paper has met with both skepticism and hype.  Media declares that “arsenic loving bacteria” have been found, which is more than the original claim.  Quoting the authors: “..GFAJ-1 is not an obligate arsenophile and it grew considerably better when provided with P..”, meaning, the bacteria merely coped with the adverse conditions provided, and managed to survive by some mechanisms, which are not inherent.  Given a choice of phosphorous and arsenic, they would “love” phosphorous more, and the media hysteria would subside.

Some others doubt that the arsenic may have been found in the vacuoles and therefore contaminated the DNAs that were being tested and await further proof.

An important conclusion that can be made from these results is that under a different set of conditions than commonly seen on earth, a different set of life forms can potentially arise (“alternate life”) and offer more ground for search of other forms of alternate life both within earth and without.

Perhaps feeding bacteria with silicon (not to be confused with "silicone" which is a polymer funded by Baywatch) instead of carbon could incorporate silicon in its DNA? 

But then, we’ve already done it  haven’t we?

 

Our own silicon man - Enthiran

 

 Post Script: Dude's more detailed post on the discovery is here.

Comments

[SteveB]

I thought the authors did themselves a disservice with the press conference and allowing all the hyperbole, because it really undermines a pretty cool finding about how tenacious life can be and how we've learned something about bending/breaking fundamental rules of biology.

[Lakshmi]

Steve, the media coverage irritated me as well. The hype masked the elegance of the fact. Nature (http://www.nature.com/news/2010/101202/full/news.2010.645.html) had the most balanced account of the development.

[Arvind]

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Yet a few have developed strategies to include arsenic into their metabolic cycle, so that instead of killing them, arsenic actually fuels their living. Good Luck

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So fun article is! I know more from it.

[freelance writing]

life can be and how we've learned something about bending/breaking fundamental rules of biology.

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Great article! All too often a blog will get off-topic and have a hard time returning from the abyss.

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