Refining the Genetic Alphabet: A Late-Period Selection Pressure?

Abstract

The transition from genomic ribonucleic acid (RNA) to deoxyribonucleic acid (DNA) in primitive cells may have created a selection pressure that refined the genetic alphabet, resulting from the global weakening of the Nglycosyl bonds. Hydrolytic rupture of these bonds, termed deglycosylation, leaves an abasic site that is the single greatest threat to the stability and integrity of genomic DNA. The rates of deglycosylation are highly dependent on the identity of the nucleobases. Modifications made to the bases, such as deamination, oxidation, and alkylation, can further increase deglycosylation reaction rates, suggesting that the native bases provide optimum N-glycosyl bond stability. To protect their genomes, cells have evolved highly specific enzymes called glycosylases, associated with DNA repair, that detect and remove these damaged bases. In RNA, however, the occurrence of many of these modified bases is deliberate. The dichotomous behavior that cells exhibit toward base modifications may have originated in the RNA world. Modified bases would have been advantageous for the functional and structural repertoire of catalytic RNAs. Yet in an early DNA world, the utility of these heterocycles was greatly diminished, and their presence posed a distinct liability to the stability of cells' genomes. A natural selection for bases exhibiting the greatest resistance to deglycosylation would have ensured the viability of early DNA life, along with the recruitment of DNA repair.

On the Origin of the Canonical Nucleobases: An Assessment of Selection Pressures across Chemical and Early Biological Evolution

“…[42b] As early life evolved, so did the nature of the bases as new environmental and functional pressures emerged. [65] Alternative viewpoints have been put forward suggesting that selection of the native bases coincided with the emergence of RNA from the prebiotic environment. [10c,44] This scenario appears to offer a simpler explanation for the origin of the nucleic acid bases.…”

“…A recent hypothesis has detailed the possibility of one such selection pressure that implicates the role of N -glycosyl bonds in the early DNA world. [65] While the polymeric stability of DNA is far superior to that of RNA, [66] it is well established that DNA suffers from weaker N -glycosyl bonds. [22,67] The hydrolysis of these linkages (i.e., depurination/depyrimidination) leaves an abasic site in the sugar-phosphate backbone of DNA that, unless repaired, is well known to not only be mutagenic, but also to lead to the cleavage of genetic material (Figure 10).…”

“…[68] It was proposed that, given the vital role N -glycosyl bonds have on the overall stability of the genetic material, a strong selection pressure might have played out in the early DNA world that facilitated the selection of bases exhibiting the most hydrolytically resistant glycosidic bonds. [65] …”

Orotidine‐Containing RNA: Implications for the Hierarchical Selection (Systems Chemistry Emergence) of RNA

“…Rather, considering what has been argued by others and succinctly stated by Joyce, “The evolution of RNA is likely to have played an important role in the very early history of life on Earth but it is doubtful that life began with RNA. Consideration of what came before RNA must take into account relevant information from geochemistry, prebiotic chemistry and nucleic acid biochemistry”, and by Rios and Tor, “The selection of the native bases did not occur in any one hypothetical period. It is more likely that a continuous process of refinement directed their selection throughout prebiotic and early biotic epochs”, it appears that RNA is a destination and not a destiny.…”

Base‐Pairing Properties of a Structural Isomer of Glycerol Nucleic Acid

“…[4,20] The search for structurally minimal ("simple") informational systems need not be constrained to the set of natural nucleobases as the recognition elements. These canonical nucleobases may represent a "functional optimum" [21] with respect to the phosphate backbone, as the product of evolutionary selection, [22] but this also allows for the possibility that there may be other primordial recognition elements that could function in conjunction with simple, prebiotic backbones. [1] Thus, the search for-and mapping of-primordial information systems could encompass a wider variety of constituents, which are compatible with heterotrophic and/or autotrophic environments.…”