[Show abstract][Hide abstract] ABSTRACT: The formation of canonical base pairs through Watson-Crick hydrogen bonding sits at the heart of the genetic apparatus. The specificity of the base pairing of adenine with thymine/uracil and guanine with cytosine preserves accurate information for the biochemical blueprint and replicates the instructions necessary for carrying out biological function. The chemical evolution question of how these five canonical nucleobases were selected over various other possibilities remains intriguing. Since these and alternative nucleobases would have been available for chemical evolution, the reasons for the emergence of this system appear to be primarily functional. While investigating the base-pairing properties of structural nucleic acid analogs, we encountered a relationship between the pK(a) of a series of nonstandard (and canonical) nucleobases and the pH of the aqueous medium. This relationship appeared to correspond with the propensity of these molecules to self-assemble via Watson-Crick-type base-pairing interactions. A simple correlation of the "magnitude of the difference between the pK(a) and pH" (pK(a)-pH correlation) enables a general prediction of which types of heterocyclic recognition elements form hydrogen-bonded base pairs in aqueous media. Using the pK(a)-pH relationship, we can rationalize why nature chose the canonical nucleobases in terms of hydrophobic and hydrophilic interactions, and further extrapolate its significance within the context of chemical evolution. The connection between the physicochemical properties of bioorganic compounds and the interactions with their aqueous environment directly affects structure and function, at both a molecular and a supramolecular level. A general structure-function pattern emerges in biomolecules and biopolymers in aqueous media near neutral pH. A pK(a) - pH < 2 generally prompts catalytic functions, central to metabolism, but a difference in pK(a) - pH > 2 seems to result in the emergence of structure, central to replication. While this general trend is observed throughout extant biology, it could have also been an important factor in chemical evolution.
Accounts of Chemical Research 04/2012; · 20.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The general notion of an "RNA World" is that, in the early development of life on the Earth, genetic continuity was assured by the replication of RNA and genetically encoded proteins were not involved as catalysts. There is now strong evidence indicating that an RNA World did indeed exist before DNA- and protein-based life. However, arguments regarding whether life on Earth began with RNA are more tenuous. It might be imagined that all of the components of RNA were available in some prebiotic pool, and that these components assembled into replicating, evolving polynucleotides without the prior existence of any evolved macromolecules. A thorough consideration of this "RNA-first" view of the origin of life must reconcile concerns regarding the intractable mixtures that are obtained in experiments designed to simulate the chemistry of the primitive Earth. Perhaps these concerns will eventually be resolved, and recent experimental findings provide some reason for optimism. However, the problem of the origin of the RNA World is far from being solved, and it is fruitful to consider the alternative possibility that RNA was preceded by some other replicating, evolving molecule, just as DNA and proteins were preceded by RNA.
Cold Spring Harbor perspectives in biology 08/2010; 4(5). · 9.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The origin of RNA is one of the most formidable problems facing prebiotic chemists. We consider RNA as a product of evolution, as opposed to the more conventional view of RNA as originally being the product of abiotic processes. We have come to accept that life's informational polymers have changed in chemical structure since their emergence, which presents a quandary similar to the paradox of "My Grandfather's Axe". Here, we discuss reasons why all contemporary components of RNA-the nucleobases, ribose, and phosphate-are not likely the original components of the first informational polymer(s) of life. We also evaluate three distinct models put forth as pathways for how the earliest informational polymers might have assembled. We see the quest to uncover the ancestors of RNA as an exciting scientific journey, one that is already providing additional chemical constraints on the origin of life and one that has the potential to produce self-assembling materials, novel catalysis, and bioactive compounds.
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.