Sequence self-selection by the network dynamics of random ligating oligomer pools
[thesis]
Patrick Kudella, Dieter Braun
2021
One problem on the research on the Origin of Life is the step from short oligomers with random sequence of bases to longer, active complexes like ribozymes. Chemistry and non-equilibrium physics have found pathways for the formation of short strands, mediated by activated nucleotides or activation agents. It has also been shown, that medium length autocatalytically active complexes can form reaction networks necessary for downstream reactions and the emergence of more sophisticated systems. The
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... intermediate step is difficult though: Short random sequences need to be extended, while introducing a reduction of sequence entropy, that does not inhibit double-stranded complex formation. This pre-selection step is necessary due to the vast sequence space of oligomer strands and must conform to an Origin-of-Life-like environment. The ancient reactions only depended on the inherent parameters of the oligomer strands such as the hybridization to double-stranded complexes and basic physical mechanisms such as temperature changes. Although short strands likely emerged by a non-templated polymerization-like extension mechanism, passing sequence information from one strand to another is assumed essential in longer strands. Chemical ligation is probable in the context of the Origin of Life, but the yield and specificity is known to be low. As a model for said mechanism, this study utilizes an evolved DNA ligase to facilitate the ligation reaction of the model-oligomer (DNA) without introducing a sequence bias. After 1000 temperature cycles, necessary for the dissociation and rehybridization of elongated strands, the resulting reaction products showed several distinct features of selection. Compared to random strands of the same length, the set of emerging reaction products have a significantly reduced sequence entropy. The emerging strands can be categorized in two groups: A-type and T-type strands with a ratio about 70:30 % of each base. As strands can only act as a template or substrate in the templated ligation reaction whe [...]
doi:10.5282/edoc.27817
fatcat:f2fwywjlnjby7o2cl3olfogodq