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NatureScience

RNA-Like Molecules Found to Self-Assemble into Gene-Like Material – Discovery May Be Key to the Origin of Life

 

proto-RNA self-assembling into genetic material
Proto-RNA? Chemicals known as TAPAS and CA (left) assemble together forming rosettes (middle) that then stack into genelike chains (right). Credit: B.J. Cafferty et al., JACS (2013)

In the great quest to uncover the secrets to the origin of life on Earth — a discipline referred to as biogenesis theory — there remains a profound (unanswered) question: how do “living” molecules arise from non-living ones? For, to answer such a question means making a distinction between different states of molecular organization. The question is almost metaphysical in nature — for it requires one to ponder the very definition of ‘Life’; it is nearly impossible to pinpoint a particular stage (or molecular structure) in the genesis of living matter and say this is now “alive”, when previously, it was “non-living” (e.g., Is it only the cell that is alive? What about mitochondria which also have DNA? What about the ribosomes that translate RNA messages into proteins?, etc.)

But there are a few requirements for living matter that scientists do recognize; such living molecules must possess two fundamental features: they must be capable of “self-organization” (also called “self-assembly”) under the right environmental conditions, and, they must be capable of self-replication. This last feature is tricky, since it implies that there is some form of “molecular memory”, or information coding, at work, such that these special molecules can remember how to copy themselves.

The RNA World hypothesis

The most promising candidate molecules here are RNA (ribonucleic acid) molecules which are both simpler than DNA molecules and more powerful catalysts for molecular interactions. Indeed, RNA-based enzymes (i.e., the RNA polymerases) are necessary for DNA replication. Many biologists believe that some form of RNA — or precursors to RNA — had to evolve first, before the more complex DNA molecule could appear. This view is known as the ‘RNA World’ hypothesis.

But, there’s one big problem with the RNA World hypothesis; the building blocks of RNA — the nucleoside bases cytosine (C), guanine (G), adenine (A) and urasil (U) — do not normally assemble themselves into longer chains to form the genetic structures we associate with living molecules.

This has led many scientists to posit precursors to these RNA bases — proto-RNAs — that must have evolved first. According to Nicholas Hud, a chemist at the Georgia Institute of Technology (Georgia Tech) in Atlanta, “RNA is so perfect today that it has to be the product of evolution”

The Experiments with “Proto-RNA” Molecules

To test this theory, Georgia Tech researchers, collaborating with colleagues from the Institute for Research in Biomedicine in Barcelona, Spain, began a series of experiments with two key proto-RNA candidate molecules: cyanuric acid (CA) and triaminopyrimidine (TAP). The latter molecule belongs to a family of chemicals called pyrimidines of which the RNA bases C and U are members. CA is also structurally related to the pyrimidines. Earlier research had shown that these molecules spontaneously formed ring-like structures called rosettes — when immerse in an organic solvent medium. Successive rosettes would stick together to form stacks — compound structures that bear some resemblance to how genetic material is built up from simpler, repetitive structures.

However, the research team found that, in water, TAP and CA simply clump together into ribbons and sheets and then fall out of solution — what’s known as the “hydrophobic effect” — which is not a good result for molecules that supposedly give rise to RNAs (which must also store genetic information).
Testing these molecules in water is significant, given the notion of a “primordial soup” — the primordial, watery ecosystem (a pond, lake, tide pool, or even deep sea vent) that is posited to have been the matrix of living molecules. Yet, when placed in water, these would-be RNA precursors failed to form into more complex structures.
But further testing led researcher to a solution for this “solution problem.” The team devised a chemical structure — a short “tail” — that, when attached to TAP, stimulated it to assemble with with CA to form the rosette structures they were looking for. The new molecule was dubbed TAPAS. further, the rosettes then began stacking one atop the other — forming longer, more complex chains of gene-like material. Some of these chains possessed over 18,000 individual units of TAPAS and CA. The researchers described this as “highly cooperative self-assembly.”
Quoting from the published report (abstract):
“Two weakly interacting low-molecular-weight monomers (cyanuric acid and a modified triaminopyrimidine) are shown to form extremely long supramolecular polymer assemblies that retain water solubility. The complete absence of intermediate assemblies means that the observed equilibrium is between free monomers and supramolecular assemblies…[content edited]
The results of our study have implications for the design of new self-assembling structures and hydrogel-forming molecules and may provide insights into the origin of the first RNA-like polymers.”
What’s Next for Biogenesis Experiments?
So, researchers have, at last, achieved molecular self-assembly (of “proto-RNA”) in water.
However, what still remains to be seen is whether or not this two-molecule, self-assembly system can somehow encode information — the molecular memory requirement of living matter — which would potentially drive these molecules towards a structures resembling actual RNA.
And, even if this feat is achieved, it will not prove that this is how life arose from the primordial soup…but it will demonstrate one path that key molecules may have taken on the long journey of becoming living matter.
Scientific team members included: Brian J. Cafferty, Isaac Gállego, Michael C. Chen, Katherine I. Farley, Ramon Eritja, and Nicholas V. Hud.

The paper entitled ‘Efficient Self-Assembly in Water of Long Noncovalent Polymers by Nucleobase Analogues’ was published February 8th in the Journal of the American Chemical Society.

For further reading on the subject of biogenesis, check out my earlier article In Search of Ancient Alien Microbes & the Origin of Life.

Main Reference for this post: ‘Self-Assembling Molecules Offer New Clues on Life’s Possible Origin’ by Robert F. Service

Top Image: (RNA-like molecules self-assemble into gene-like structures in water); Credit: B.J. Cafferty et al., JACS (2013)

 




2 comments
  1. Георгий

    Thermodynamics of
    origin of life: Why is there life?

    The transition between the animate
    and inanimate matter is a slow. It was predestined by the action of
    “thermodynamic principle of the substance stability” which describes
    the forward and backward linkages at the transmission of information between
    structural hierarchies during the chemical and biological evolution.

    http://gladyshevevolution.wordpress.com/

    See: Thermodynamics and the
    emergence of life.

    The phenomena of life can be
    explained on the basis of quasi-equilibrium hierarchical thermodynamics of
    dynamic systems which stands at the solid foundation of thermodynamics of JW
    Gibbs. Theory can be constructed without using the concept of dissipative
    structures of I. Prigogine and his ideas about negentropy.

    http://www.youtube.com/watch?v=CYr1G5TZO50

    From the point of view of
    thermodynamics, the phenomenon of life is defined as: “Life is the process
    the existence of the constantly renewed
    polyhierarchical structures during cycles of transformation of labile
    chemical substances in the presence of liquid water on the planet.”

    Sincerely,

    Georgi Gladyshev

    Professor of Physical Chemistry

    1. Michael Ricciardi

      Professor

      Thanks for your comment and erudite explanation.

      I am familiar with Ilya Prigogine’s work and theory of ‘Dissipative Structures’ (I also interviewed him back in 1998, after the publication of his book ‘The End of Certainty’) but less so with that of JW Gibbs, though I am aware that he pioneered the field of statistical mechanics (a discipline in which Prigogine was deeply involved).

      For the reader: “statistical mechanics” defines the laws of thermodynamics (i.e., the behavior of heat/energy as it interacts with physical matter) as “consequences of the statistical properties of large ensembles of particles.”

      Which sounds quite scientific and all, but it may not be clear to the reader how this applies to the origin of life.

      You make three assertions here:

      1] That the transition between inanimate and animate (life)…was predestined by the action of
      “thermodynamic principle of the substance stability” …(a process which describes the) “forward and backward linkages at the transmission of information between structural hierarchies during the chemical and biological evolution.”

      2] that “the phenomena of life can be explained on the basis of quasi-equilibrium hierarchical thermodynamics of dynamic systems”

      3] the phenomenon of life is defined as: “Life is the process [of] the existence of the constantly renewed
      polyhierarchical structures during cycles of transformation of labile chemical substances in the presence of liquid water on the planet.”

      First, there is a great deal of expert nomenclature/jargon here, and the average reader might simply capitulate without understanding.

      Second, while I would concur that each of these assertions describes accurately the processes being invoked (which are used to explain Life’s origins), nonetheless, none of these (by themselves or taken together) fully and CLEARLY describers how life evolves from “inanimate” to “animate”…if they did do so, biogenesis researchers would simply take these descriptions, as is, and apply them to a cocktail of atoms in some appropriate mixture, and create Life…voila!…it would be front page news all over the world.

      The Closest they have ever come to this is the Miller-Urey experiments from the late 1950’s…and these only succeeded in making adenine molecules, but which did not replicate. More recent work by Robertson and Scott have demonstrated ribozyme-catalyzed self-assembly of RNA (via L1-Ligases), and, Lincoln discovered “cross-catalyzing enzymes” that continuously replicate themselves…but none have achieved actual “life” apart from duplicating some mechanical function(s). (see linked-to article in the article above)

      The fact is, while Life — including the ‘transition from inanimate to animate” matter — is surely governed by thermodynamics (on the fundamental level of what is physically possible), still, on these higher levels of organization (the “hierarchies” that you point out), there are new, emergent properties and phenomena (for example, genes and gene networks, epigenetic networks/the transcritpome, etc.) on each of these levels…properties that have yet to be duplicated by a strict application of the laws that you describe…this remains to be seen, as they say.

      At least, I know of no such demonstrated application of the laws of thermodynamics (whether dynamic system or classical) resulting in self-organizing and self-replicating “Living” matter

      Michael R.

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