Thursday, May 8, 2014
Amazing! Bacteria have been cajoled into accepting two new letters into their genetic code! But what are those letters - in chemical terms?
Yes, there's an exciting item of science news this morning - the best I've seen in months. I shan't try to write a lengthy preamble, there being no need, given that there are journos out there who have done a reasonable job already (and get paid for it!)
See for instance this write-up in the Independent.
New Life: Scientists create first semi-synthetic organism with alien DNA
But it's very frustrating to have new chemicals referred to by abbreviations, without knowing what the letters stand for, or being given structural chemical formulae.
The two new bases in question, shortlisted from scores of experimental candidate molecules, screened over many years of study, are "d5SICS " and " dNaM ".
While I haven't got a fix on the names (but could make an educated guess) I have discovered a highly detailed paper on their chemistry that gives structural formulae.
The graphic above shows the two new letters and their abbreviations (d5SICS and dNaM). They have been shown above as the base-pair, capable of providing a third type of rung on the DNA double helix, additional to Mother Nature's G-C and A-T base pairs and two new letters in the genetic code, making 6 instead of the present 4.
If you know a little chemistry, you should be able to spot features in both the new bases that show they are alien to Planet Earth. The first (d5SICS) has a sulphur atom attached to the ring system instead of oxygen. What's more, one of the two rings in that cyclic structure lacks nitrogen - it's a benzene ring - whereas the authentic purine bases like adenine and guanine have nitrogen atoms in both rings. The second (dNAM) lacks nitrogen in both those rings, which are simply two fused benzene rings, i.e. naphthalene.
I'll add structures of authentic adenine and cytosine for comparison here later.
So, these very clever and, by all accounts, dedicated scientists, have been able to create entirely new base pairs that mimic the real thing, and which have all kinds of potential for engineering new life forms (yes, they have considered safety aspects and have a strong case for thinking that any new organism would not be able to escape from the lab and multiply, unless accompanied by a personal chef doling out daily supplements of the new exotic bases).
What I find particularly fascinating from a quick read is that the two new bases form a base-pair in DNA ( a "rung" of the ladder) without needing to form hydrogen bonds with each other. Those familiar with DNA lore - or who have read James Watson's "The Double Helix" - will know the importance that was attached to H-bonding between DNA base pairs in the model-building that finally yielded the elegant and stable helical structure (pyrimidine AT-base pairs forming two hydrogen bonds, purine C-G base pairs forming three). The new "X-Y" base pair (for want of a better term) is essentially proclaiming - "Look, no hands!".
Oh, and both partners resemble "two-fused ring" purines, whereas the AT and CG base pairs are one purine-one pyrimidine, which is two-fused ring to single ring only. More later when I've had time to pore over these new bases, and maybe find their full chemical names.
In fact (late addition) yesterday's splendid article in Chemistry Today shows that the new exotic bases pair up by an entirely different mechanism - hydrophobic bonding (which relies purely on the ubiquitous albeit weak interaction between molecules known as Van der Waal forces ("flickering dipoles"). Standard hydrogen-bonding (dashed lines) is shown below for reference.
Here's a link to the New Scientist write-up.
Update: My comment just this minute posted to the Guardian:
The systematic name of d5SICS, obtained from the chemical's supplier (Berry Associates, no relation) is as follows:
That gives no clue as to how d5SICS was arrived at, though undoubtedly an abbreviation of the much shorter 'trivial' name. The "S" may refer to sulphur, aka sulfur, which in the systematic name is "thione".
See also greenfluorescentblog (there's someone else who, in common with me, seems frustrated not knowing what the letters stand for).
We live in interesting times...
Whether this breakthrough has immediate prospects of practical spin-off (new drugs etc) remains to be seen. There are grounds for thinking otherwise. But what it shows clearly is that the evolution of life on Earth, and probably elsewhere in the Universe, did not depend on the chance supply and utilization of 4 highly specific nucleic acids, capable of self-assembling into a double-helix. The fact that these two novel bases, ones that do not even have the wherewithal to form hydrogen bonds between base-pairs, suggests that the chemistry is not quite as critical as might previosly have been thought, and indeed raises the probability of there being extraterrestrial life, maybe based on nucleic and DNA-like double helices. It could be a different type of base, or bases, and possibly involve more than 4 (though 4 is more than sufficient to code for our 20 or so essential amino acids that are adequate to create the amazing biodiversity that we see on our amazing blue planet (and that's not counting the 98% of species that once thrived and which through climate change, asteroid impacts etc are now extinct).
Why our 4 particular nucleic acids? That was a topic I addressed on this site well over 4 years ago.