Emergence of Homochirality Via Template-Directed Ligation in an RNA Reactor

RNA in extant biological systems is homochiral – it consists exclusively ofD-ribonucleotides rather than L-ribonucleotides. How the homochirality of RNAemerged is not known. Here, we use stochastic simulations to quantitativelyexplore the conditions for RNA homochirality to emerge in the prebioticscenario of an `RNA reactor', in which RNA strands react in a non-equilibriumenvironment. These reactions include the hybridization, dehybridization,template-directed ligation, and cleavage of RNA strands. The RNA reactor iseither closed, with a finite pool of ribonucleotide monomers of bothchiralities (D and L), or the reactor is open, with a constant inflow of aracemic mixture of monomers. For the closed reactor, we also consider theinterconversion between D- and L-monomers via a racemization reaction. We firstshow that template-free polymerization is unable to reach a high degree ofhomochirality, due to the lack of autocatalytic amplification. In contrast, inthe presence of template-directed ligation, with base pairing and stackingbetween bases of the same chirality thermodynamically favored, a high degree ofhomochirality can arise and be maintained, provided that the non-equilibriumenvironment overcomes product inhibition, for instance via temperature cycling.Furthermore, if the experimentally observed kinetic stalling of ligation afterchiral mismatches is also incorporated, the RNA reactor can evolve towards afully homochiral state, in which one chirality is entirely lost. This ispossible, because the kinetic stalling after chiral mismatches effectivelyimplements a chiral cross-inhibition process. Taken together, our modelsupports a scenario, where the emergence of homochirality is assisted bytemplate-directed ligation and polymerization in a non-equilibrium RNA reactor.