The central dogma of biological homochirality: How does chiral information propagate in a prebiotic network?

Abstract

Biological systems are homochiral, raising the question of how a racemic mixture of prebiotically synthesized biomolecules could attain a homochiral state at the network level. Based on our recent results, we aim to address a related question of how chiral information might have flowed in a prebiotic network. Utilizing the crystallization properties of the central ribonucleic acid (RNA) precursor known as ribose-aminooxazoline (RAO), we showed that its homochiral crystals can be obtained from its fully racemic solution on a magnetic mineral surface due to the chiral-induced spin selectivity (CISS) effect [Ozturk et al., arXiv:2303.01394 (2023)]. Moreover, we uncovered a mechanism facilitated by the CISS effect through which chiral molecules, such as RAO, can uniformly magnetize such surfaces in a variety of planetary environments in a persistent manner [Ozturk et al., arXiv:2304.09095 (2023)]. All this is very tantalizing because recent experiments with tRNA analogs demonstrate high stereoselectivity in the attachment of L-amino acids to D-ribonucleotides, enabling the transfer of homochirality from RNA to peptides [Wu et al., J. Am. Chem. Soc. 143, 11836 (2021)]. Therefore, the biological homochirality problem may be reduced to ensuring that a single common RNA precursor (e.g., RAO) can be made homochiral. The emergence of homochirality at RAO then allows for the chiral information to propagate through RNA, then to peptides, and ultimately through enantioselective catalysis to metabolites. This directionality of the chiral information flow parallels that of the central dogma of molecular biology—the unidirectional transfer of genetic information from nucleic acids to proteins [F. H. Crick, in Symposia of the Society for Experimental Biology, Number XII: The Biological Replication of Macromolecules, edited by F. K. Sanders (Cambridge University Press, Cambridge, 1958), pp. 138-163; and F. Crick, Nature 227, 561 (1970)].

Chirality-induced avalanche magnetization of magnetite by an RNA precursor

“…Last but not least, the emergence of homochirality at the stage of RAO can allow for the efficient transfer of homochirality through RNA to peptides due to the high stereoselectivity in the attachment of L-amino acids to tRNA analogs composed of D-ribonucleotides 4 , 39 . However, it is important to acknowledge that, based on current evidence, RAO serves as a precursor solely to RNA pyrimidines.…”

“…If a route to RNA purines from RAO is also discovered, the biological homochirality problem can be simplified by focusing on the production of a single shared RNA precursor with uniform chirality. In such a scenario, once homochirality is achieved in RAO, it can be effectively transferred from RNA to peptides, and eventually, through enantioselective catalysis, to metabolites—therefore to the entire prebiotic network 4 . With these features, RAO is a promising prebiotic compound which can play a central role in the emergence of biological homochirality.…”

Stabilization of Prebiotic Vesicles by Peptides Depends on Sequence and Chirality: A Mechanism for Selection of Protocell-Associated Peptides

“…If the chiral-induced spin selectivity effect was responsible for the homochirality of Leu-Leu, the preferred handedness would have depended on the direction of the magnetic field. In addition, if peptide chirality arose from chiral precursors of d -ribonucleic acids that, in turn, coded for l -peptides, as Ozturk et al further suggest, then the mechanism that we have identified here is a potential link between a proto-genome, compartmentalization, the origin of chirality, and Darwinian selection of protocells containing chiral molecules.…”