Is Watson-Crick pairing more ancient than DNA?
"It has not escaped our notice that the specific pairing we have postulated immediately suggests a possible copying mechanism for the genetic material." This famous sentence concludes the 1953 Nature paper in which James Watson and Francis Crick first reported the physical structure of DNA. Thus, pairs of DNA polymer chains can stitch themselves together to form the Watson-Crick double helix if they have matching sequences of their selectively bonding side groups, the “bases” adenine (A), cytosine (C) guanine (G), and thymine (T).
The Watson-Crick pairing rule, that a duplex is formed by the bases binding selectively, A only with T and C only with G, is indeed at the root of the storage and transmission of genetic information in life, as they proposed, enabling our understanding of the evolution of living beings, and the development of many diagnostic and therapeutic biotechnologies. Although this structure and function of the polymeric DNA (and RNA) double-helix has been studied for decades, its origin and first appearance as the basis of life remains a mystery.
Up until now it has been supposed that Watson-Crick base pairing is a DNA polymer phenomenon, depending on the linking of the side group bases into chains. However, a study published this week in PNAS by research groups coordinated by Prof. Tommaso Bellini at the University of Milan and by Prof. Noel Clark at the University of Colorado, Boulder (USA), shows that the DNA double helix can form in aqueous solutions of unpolymerized single nucleic acid bases. The collaboration found that certain mixtures of the nucleic acid monomers Adenosine triphosphate (ATP), with CTP, GTP, and TTP at high concentration and low temperature can exhibit a phase transition in which these small molecules spontaneously form the duplex base-paired and -stacked structures of biopolymer nucleic acids.
Remarkably, in this self-assembly, a liquid crystal phase of duplex columnar molecular stacks, Watson-Crick selectivity is also operative: the most stable duplexes and therefore liquid crystals in mixed solutions of A, C, G, and T single bases are found in the A–T and C–G combinations that also stabilize the polymer double-helix.
To paraphrase Watson and Crick, this observation immediately suggests that polymeric DNA may have evolved from monomeric DNA in the context of selecting and ordering molecules capable of promoting liquid crystal growth, a primitive prebiotic process.
This notion is in fact supported by earlier experiments of the Bellini-Clark collaboration which have shown that ordering short duplexed DNA oligomers into a columnar liquid crystal phase can, in the presence of appropriate chemistry, promote their ligation into longer chains. Extending the chain length in turn stabilizes the liquid crystal ordering, creating the potential for positive feedback by which the liquid crystal state can select, organize, and modify molecules to promote its own growth, conditions which create an autocatalytic cycle.
The findings thus suggest a pathway of liquid crystal autocatalysis in which the essential structural characteristics of polymeric duplex DNA can spontaneously arise from small molecules, as potential mode of origination of DNA-like molecules in the prebiotic universe.
The research team included Tommaso Fraccia, Marco Todisco and Giuliano Zanchetta on the Italian side, and Gregory Smith, Chenhui Zhu and Emily Hayden in the US.
Backbone-free duplex-stacked monomer nucleic acids exhibiting Watson–Crick selectivity
Gregory P. Smith, Tommaso P. Fraccia, Marco Todisco, Giuliano Zanchetta, Chenhui Zhu, Emily Hayden, Tommaso Bellini, and Noel A. Clark
PNAS July 2, 2018. 201721369