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O'Flaherty, D.

Publications and source records attributed to O'Flaherty, D..

2 recordsLinked to original sources

Thermal oscillations enable reshuffling of genetic material in a primitive cell cycle

Self-assembling single-chain amphiphiles available in the prebiotic environment likely played a fundamental role in the advent of primitive cell cycles. However, the instability of prebiotic fatty acid-based membranes to temperature and pH seems to suggest that primitive cells could only host prebiotically-relevant processes in a narrow range of non-fluctuating environmental conditions. Here we propose a novel primitive cell cycle driven by environmental fluctuations, which enable the generation of daughter protocells with reshuffled content. A reversible membrane-to-oil phase transition accounts for the dissolution of fatty acid-based vesicles at high temperatures, and the concomitant release of genetic content. At low temperatures, fatty acid bilayers reassemble and encapsulate reshuffled genetic material in a new cohort of protocells. Notably, we find that our disassembly/reassembly cycle drives the emergence of functional RNA-containing primitive cells from parent non-functional compartments. Thus, by exploiting the intrinsic instability of prebiotic fatty acid vesicles, our results point at an environmentally-driven tunable primitive cell cycle, which supports the release and reshuffle of protocellular genetic and membrane components, potentially leading to a new generation of protocells with superior traits. In the absence of protocellular transport machinery, the environmentally-driven disassembly/assembly cycle proposed herein would have supported genetic content reshuffling transmitted to primitive cell progeny, hinting at a potential mechanism important to initiate Darwinian evolution of early lifeforms.

biophysics↗

Assembly of a functional ribozyme from short oligomers by enhanced non-enzymatic ligation

The non-enzymatic replication of the primordial genetic material is thought to have enabled the evolution of the first ribozymes, leading to early forms of RNA-based life. However, the reported rate of chemical RNA ligation is extremely slow. Here we show that the rate of ligation can be greatly enhanced by employing a 3'-amino group at the 3'-end of each oligonucleotide, in combination with an N-alkyl imidazole organocatalyst. These modifications allow the rapid copying of long RNA templates by multi-step ligation of tetranucleotides, as well as the assembly of long oligonucleotides from short template splints. Our work shows that a functional RNA ligase ribozyme can be assembled from relatively short oligonucleotides, demonstrating a transition from non-enzymatic ligation to enzymatic ligation. We suggest that the genomes of primitive protocells could have consisted of relatively easily replicated oligonucleotides as short as 10 to 12 nucleotides in length.

synthetic biology↗