Random-sequence genetic oligomer pools display an innate potential for ligation and recombination

Abstract

Recombination, the exchange of information between different genetic polymer strands, is of fundamental importance in biology for genome maintenance and genetic diversification and is mediated by dedicated recombinase enzymes. Here, we describe an innate capacity for non-enzymatic recombination (and ligation) in random-sequence genetic oligomer pools. Specifically, we examine random and semi-random eicosamer (N20) pools of RNA, DNA and the unnatural genetic polymers ANA (arabino-), HNA (hexitol-) and AtNA (altritol-nucleic acids). While DNA, ANA and HNA pools proved inert, RNA (and to a lesser extent AtNA) pools displayed diverse modes of spontaneous intermolecular recombination, connecting recombination mechanistically to the vicinal ring cis-diol configuration shared by RNA and AtNA. Thus, the chemical constitution that renders both susceptible to hydrolysis emerges as the fundamental determinant of an innate capacity for recombination, which is shown to promote a concomitant increase in compositional, informational and structural pool complexity and hence evolutionary potential.

Impact of substrate-template stability, temperature, phosphate location, and nick-site base pairs on non-enzymatic DNA ligation: Defining parameters for optimization of ligation rates and yields with carbodiimide activation

“…These findings are similar to those observed by Carrierio, and Damha (9) in which the G pT ligation site gave 10% yield, while T pT site gave 66% yield, and others (20,21), that have also found that pyrimidinepyrimidine base flanking is better than other base flanking compositions. average of two or three independent experiment replicates; with error bars representing the range of values measured.…”

Limited Sequence Diversity Within a Population Supports Prebiotic RNA Reproduction

“…Here, we constructed and analyzed an RNA-based catalytic reaction model under prebiotically possible template-directed recombination and ligation. These modes of reproduction would have been more accessible to emergent polymeric pre-life than template-directed replication [17,18]. Using this system, we showed that at least in a subset of RNA population, sequence diversity within the population is a key factor to trigger RNA reproduction through iterative reactions.…”

“…These reactions are nearly energy-neutral but potentially irreversible if driven by the formation of stable secondary structures, and hence are prebiotically facile. Recombination of RNA oligomers has been recently demonstrated to occur readily, by a number of mechanisms [17,18]. The products could serve as a template for reactions that in turn catalyze their own production (i.e., autocatalytic reproduction).…”

“…Another possible reaction for reproduction is template-directed ligation, which conjugates two sequences (e.g., 8-mer + 8-mer → 16-mer). Although template-directed ligation has been extensively examined [9,17,19,20], the availability of required pre-activated fragments in prebiotic conditions is arguable.…”

Thresholds in Origin of Life Scenarios

“…Finally, the transition scenario toward existence of a sustainable replicase may be revised by considering different polymer generation processes anterior to the replicase regime. Polymer generation could have been enhanced by catalysis of polymerization ( Hazen and Sverjensky, 2010 ), ligation ( Mutschler et al., 2018 ), or recombination ( Blokhuis and Lacoste, 2017 ), as well as by size selection ( Mizuuchi et al., 2019 ). An alternative is that autocatalytic sets could have preceded template-based replication and biased polymer populations toward longer and more functional sequences ( Vasas et al., 2012 ).…”