Homochirality is a signature of life on Earth, yet its origins remain an unsolved puzzle. Achieving homochirality is essential for a high-yielding prebiotic network capable of producing functional polymers like RNA and peptides on a persistent basis. Because of the chiral-induced spin selectivity effect, which established a strong coupling between electron spin and molecular chirality, magnetic surfaces can act as chiral agents and be templates for the enantioselective crystallization of chiral molecules. Here, we studied the spin-selective crystallization of racemic ribo-aminooxazoline (RAO), an RNA precursor, on magnetite (Fe ₃ O ₄ ) surfaces, achieving an unprecedented enantiomeric excess (ee) of about 60%. Following the initial enrichment, we then obtained homochiral (100% ee) crystals of RAO after a subsequent crystallization. Our results demonstrate a prebiotically plausible way of achieving system-level homochirality from completely racemic starting materials, in a shallow-lake environment on early Earth where sedimentary magnetite deposits are expected to be common.

Molecular evolution can be conceptualized as a walk over a 'fitness landscape', or the function of fitness (e.g., catalytic activity) over the space of all possible sequences. Understanding evolution requires knowing the structure of the fitness landscape and identifying the viable evolutionary pathways through the landscape. However, the fitness landscape for any catalytic biomolecule is largely unknown. The evolution of catalytic RNA is of special interest because RNA is believed to have been foundational to early life. In particular, an essential activity leading to the genetic code would be the reaction of ribozymes with activated amino acids, such as 5(4H)-oxazolones, to form aminoacyl-RNA. Here we combine in vitro selection with a massively parallel kinetic assay to map a fitness landscape for self-aminoacylating RNA, with nearly complete coverage of sequence space in a central 21-nucleotide region. The method (SCAPE: sequencing to measure catalytic activity paired with in vitro evolution) shows that the landscape contains three major ribozyme families (landscape peaks). An analysis of evolutionary pathways shows that, while local optimization within a ribozyme family would be possible, optimization of activity over the entire landscape would be frustrated by large valleys of low activity. The sequence motifs associated with each peak represent different solutions to the problem of catalysis, so the inability to traverse the landscape globally corresponds to an inability to restructure the ribozyme without losing activity. The frustrated nature of the evolutionary network suggests that chance emergence of a ribozyme motif would be more important than optimization by natural selection.

The very specific thermodynamic instability and kinetic stability of phosphate esters and anhydrides impart them invaluable properties in living organisms in which highly efficient enzyme catalysts compensate for their low intrinsic reactivity. Considering their role in protein biosynthesis, these properties raise a paradox about early stages: How could these species be selected in the absence of enzymes? This review is aimed at demonstrating that considering mixed anhydrides or other species more reactive than esters and anhydrides can help in solving the paradox. The consequences of this approach for chemical evolution and early stages of life are analysed.