You can find the author’s summary of Sasi’s work written in 1981 in the Johnson Material at https://singingdancingdna.com/dna-is-not-always-a-simple-double-helix/. From p24 para 4 of that summary you will find a set of critiques of Sasi’s conclusions and his 5 right and 5 left SBS structure. These critiques lay the foundations of the dynamic ASDT model which for 40 years was taken by the author to be a relatively obvious and unproblematic extrapolation of Sasi’s basic results.
As you’ll see on the Welcome and the Brief Outline pages it has only been very recently that the potential significance of the ASDT model has been made apparent by Samir Brahmachari’s first sight of it following the initial launch of the sister site (www.sidebysidedna.com). This is why this new site has been created.
REGULAR STRUCTURES?
Armed with moderate secondary/high school science the author came to understand Sasi’s work only after a great deal of effort. The papers which were key to this understanding were the Nature paper ‘Is 3′ nucleotide rigid’ ( https://sidebysidedna.com/sasisekharan-papers/ Sasisekharan Papers 8) (S8) and the Nucleic Acids Research paper ‘Theoretical Calculations….Stacking Interactions in Polynucleotides’ ( https://sidebysidedna.com/sasisekharan-papers/ Sasisekharan Papers 4) (S4). The illustrations from these are shown on this site Discussion of Sasi’s Work pp3-7.
What clicked from these two papers was that the base stacking was pragmatic to specific base sequences. This indicated that there could be no regular structure be it W-C which only has right handed stacking or Sasi’s SBS which alternates 5 bases stacked right handed and 5 bases stacked left handed. Beyond that the SBS demands that that at each left to right transition there are bases which stack inverted. Both these structures are extremely regular and specific for products of nature. They didn’t make sense given the pragmatism that Sasi’s lab data and graphs were indicating.
ENERGY GRADIENTS, PROBABILITY STATEMENTS AND DYNAMISM
The S8 paper details the energy gradients of movements around the phosphodiester bond in the backbone. The S4 paper details the stacking energy gradients in polynucleotides. In both cases Sasi made the point that the transitions were energetically feasible. This meant that transitions from right stacking to left stacking were easily achieved which was also strongly supported by Sasi’s own work showing that changes in salt concentrations can shift samples from right to left handed and are reversible (https://sidebysidedna.com/sasisekharan-papers/ Sasisekharan Papers 9 and 10). What the author took from this was that not only was the tertiary structure of the molecule irregular and pragmatic to base sequence but that at living temperatures the bases would have enough energy to be transitioning from right to left and back all the time.
The author saw the graphs of energy gradients within the phosphodiester bond showing clearly that there were paths between the 4 low energy positions with it passing easily from 1 to 2 to 3 to 4 and back again. However the energy barrier from 4 to 1 was effectively insurmountable. This makes the backbone approximate a human backbone in terms of range of movement.
The author saw the graphs of base stacking energies as probability statements with the 35o left and right minima being the most favourable and more often occupied positions while the transitions would be occupied only briefly.
This meant that beyond the structure being irregular Sasi’s results also indicated that it was fundamentally dynamic.
ASDT EMERGES
The thoughts above are laid out in the 1981 C3a summary paper. There is the idea of the molecule experiencing random left/right shifts. Over the following year or so it became apparent that a move in one base pair would trigger an associated move in the adjacent pairs. This presented as chaotic but then the idea emerged that rolling wave action would harmonise this energy, eliminating the risk of stalling and rendering it less destructive. Like this the molecule would be capable of absorbing more energy and maintaining its integrity through a very wide range of temperatures without disruption. This high thermal stability lends itself to the idea of it having emerged in organisms populating the deep sea vents. (In the novel the heroine, Tina explores this idea).
Around about 1983/4 a nature programme on tv showed a sea snake swimming. That was it. That was the motion of the molecule, the ASDT model. Subsequently there was a Spanish Dancer, Hexabranchus sanguineuswhich moved in a similar way but with spots which seemingly marked the passage of the backbone. And it was so beautiful.
BIO EVOLUTIONARY PARSIMONY
The great problem with the solutions proposed for W-C function is the need for complex associated action from a number of different molecules/enzymes (histones, isomerases) etc acting in sequence to perform core functions. The standard view of the relationship between the associated molecules and W-C DNA is to see them as activating or at least facilitating a relatively inert molecule. This is problematic because they are so undifferentiated and yet their roles are so apparently varied.
It is also problematic from a bio evolutionary standpoint. This viewpoint requires the ‘passive’ retention of a number of would be/soon to be relevant associated molecules until the evolution of the last of them allowed the whole process to become ‘live’. This doesn’t work very well in terms of bio evolutionary parsimony – Occam’s Razor.
The only other way this could have happened is if those associated molecules had evolved in functional roles in the ribonucleoprotein (RNP) world from which DNA emerged. The retained functional remnants of that world that we can be sure about include RNA and ribosomes. Well organised work would need to be done to determine if the histones and the isomerases are similarly archaic RNP remnants that were able to transfer their roles into the new DNA world.
Or else we can look at it another way entirely. If we use the ASDT model then a much more viable and parsimonious evolutionary scenario offers itself. We know that DNA has many long repeat sequences with the important coding sequences between them. In day to day template formation with the ASDT model one can envisage an overall increase in temperature causing the hydrogen bonding of the heterogeneous coding sequences to ‘break’ or open, allowing the relevant chain to offer its bases as a template with the homogeneous repeat sequences, being more thermally stable remaining closed, like zip ends.
This offers a very simple, sequence specific way to control template formation and would suggest a huge functional and therefore evolutionary advantage to a molecule capable of this that emerged in the archaic RNP world.
In this way the ASDT model offers an inherent, sequence specific functionality to DNA which is very satisfying and parsimonious. This scenario sees the transition to circular plasmids in bacteria (prokaryotes) and the development of histones etc in higher organisms (eucaryotes) as ways to stabilise this fundamentally active, inherently functional ancestral ASDT DNA molecule. This scenario turns the relationship between DNA and the associated histones, isomerases etc on its head.
THE DISTINGUISHED EMERITUS: beyond anomalies
The anomaly issue aside one of the biggest points to have emerged from the DE exchange was that at that time the author was still of the view that ASDT was a simple extension of SBS. From that perspective it made sense to ask DE a question about the relationship between SBS and the histones being turned upside down. DE reasonably said they didn’t understand the question.
The shift in the relationship with the histones etc isn’t relevant with the SBS because it isn’t any more dynamic than the W-C.
It was only after the DE exchanges that Samir had pointed out the true significance of ASDT which placed DE’s puzzlement in the right context.
But DE did observe that ‘Scientists do not spend time relitigating issues they think are settled, e.g. the structure of DNA. The only way to make them do otherwise is to confront them with evidence that contradicts their understanding of those issues. If you and your friends were to do that for the structure of DNA, you would get a hearing, and if your views were to prevail, it would indeed be a major breakthrough. That said, I think that the probability that this will occur is so close to zero as makes no difference, but a lifetime of experience has taught me never to say “never”.’
It is the author’s view that it’s possible that ASDT, together with the hugely significant findings/critiques/proposals by all the authors featured on Sean Kettle’s website may fit that bill.
Have a look at the proposal in the next section to see how.