Monday, December 20, 2010

Arsenic in DNA

Not Likely...

My main problem is the initial claim by NASA backed scientists that arsenic was present in the backbone of DNA.  From the chemistry standpoint this just didn't seem likely, especially because of what we know about hydrolysis rates of arsenate esters.  There are possible ways to get around this. But usually Nature abhors Rube Goldberg...

(a little bit inside baseball and wonky, but if you have had biology or chemistry, it should be understandable)

Others have argued that arsenate-linked DNA should have quickly fallen apart when exposed to water. Could you address this? [Q to Felicia Wolf-Simon, lead author of Science paper]

Wolfe-Simon responds with a three-part argument:
(1) No study has ever measured the rate of hydrolysis of nucleotide di and triesters of arsenate, which is what is proposed to be found in DNA.
(2) Studies of simple alkyl arsenate esters show that hydrolysis rates decrease as the size of the alkyl substitution increases (e.g. methyl, ethyl, isopropyl), probably due to steric effects.
(3) Nucleotides are even larger than simple alkyl substituents, and biomolecules are more sterically constrained.  Therefore, the rate of hydrolysis of nucleotide diesters could be much slower – perhaps slow enough that these molecules are stable in water.

In the author’s words: 
If the hydrolytic rate trend reported in Ref. 2 continues to larger-weight organics, such as those found in biomolecules, it is conceivable that arsenate-linked biopolymers might be more resistant to hydrolysis than previously thought. The small model compounds investigated in Refs. 1-3 are relatively flexible and can easily adopt the ideal geometry for water to attack the arseno-ester bond. Arsenate esters of large, biomolecules, however, are likely to be more sterically hindered leading to slower rates of hydrolysis.
Is this reasonable?  No.

The authors may be right about #1 – I couldn’t find a study that directly measured the rate of hydrolysis of arsenate nucleotides.  And they are correct about #2, at least according to the paper that I read.  But the conclusion (#3) is wrong, and the specific examples cited to support this claim are badly misinterpreted.

No.  The half-life of simple phosphate diesters in water is about 30 million years.  The half-life of the analogous arsenate diesters in water is measured in seconds

Interesting, but as one commenter reasonably points out:

Anonymous said... If the bacteria do it they do it, and if they don't they don't. The answer will be found experimentally soon enough, given all of the attention being paid. Meanwhile you argue about "angels dancing on a pin"


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