University of Groningen
Self-Replication out-of-Equilibrium
Yang, Shuo
DOI:
10.33612/diss.171627402
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Publication date:
2021
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Citation for published version (APA):
Yang, S. (2021). Self-Replication out-of-Equilibrium. University of Groningen.
https://doi.org/10.33612/diss.171627402
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Chapter 6
Chapter 6
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6.1 Research overview
The work in this thesis aims at developing systems capable of undergoing Darwinian evolution at the molecular level. Based on the synthetic self-replicator developed by our group, mutation and energy dissipation have been explored. In addition, homochirality, which is highly relevant for the origin of life has been addressed using our self-replicating systems.
In Chapter 2, mutations of self-replicators (resulting in different sizes of macrocycles) occurred when guanidinium chloride (GuHCl) was added to modify the solvent environment in which the native replicator and mutant replicator are competing for a common source. This system of mutating replicators can be expended with further important characteristics of life. As a preliminary study on out-of-equilibrium systems, in Chapter 3 we obtained and compared the kinetic constants of redox and exchange reactions in thiol-disulfide chemistry. Building on the mutating system in Chapter 2 and kinetic data from Chapter 3, Chapter 4 described a dissipative replication process: a molecularly more complex and thermodynamically less favored non-native replicator outcompeted the native replicator when both were subjected to continuous synthesis and destruction reactions. The results indicated that the complexity of a self-replicator can be increased through placing the system under out-of-equilibrium conditions, which is highly significant since complexification is an important characteristic of evolution. Additionally, we described the emergence of self-replicators with chiral selection from DCLs. The results provide a new manifestation of the interplay between self-replication and homochirality.
6.2 Perspectives
Next, perspectives on how to further study molecular Darwinian evolution are discussed. Molecular evolution requires out-of-equilibrium conditions where energy is continuously dissipated in the form of formation-destruction reaction cycles. To implement dissipative processes, thiol-disulfide chemistry was employed in this thesis and a steady state was achieved through applying redox cycles between thiols and disulfides. However, during these experiments excess oxidant needed to be added due to the different reactivities of the redox reagents, which might cause problems such as over-oxidation and limited the tunability of the system to some extent. Thereby a more efficient oxidant is needed and ideally it should have the same order magnitude of reactivity as the reductant. Further improvement can be achieved by coupling the system with computer-assisted flow control module which can detect the oxidation level of the library and adjust it to a desired level by tuning the inflow of redox reagents continuously. This engineering approach should allow us to have improved control
over the dynamic system, whose outcome might be affected by oxidation level and redox rates.
Even though in Chapter 3 we studied the kinetics of exchange and redox reactions in disulfide chemistry, the replication rate was not studied, which is equally important but difficult to investigate because the process consists of multiple phases (nucleation, elongation and breakage). Efforts should be made to uncover the mechanism of replication in more detail. If kinetic data of all the processes in out-of-equilibrium replication is obtained, then computer modelling can be utilized to analyse the complex networks and predict the optimal dissipative conditions and possible outcomes of the system.
Chapter 4 reported the complexification of self-replicators under out-of-equilibrium conditions and the resulting more complex replicator showed a higher catalytic activity toward a model reaction. However, dissipative replication and catalysis were performed separately. Next step would be the combination of these two processes, that is showing that a more complex replicator can catalyze chemical reactions (or perform other new functions) under out-of-equilibrium conditions.
Chapter 5 described the co-emergence of a homochiral pentameric self-replicator and a heterochiral trimeric self-replicator from a racemic mixture. This system is an attractive candidate for implementing out-of-equilibrium conditions. Under the right conditions dissipative replication with chiral selection and amplification may be observed.
Replication, compartmentalization and metabolism are three key features of life. In this thesis only replication was addressed and the other two features still need to be integrated. Modification of our peptide building blocks to endow them with amphiphilic properties or catalytic functionality would be promising approaches to couple replication with compartmentalization or metabolism, respectively. Last, integration of all three key features within one system might lead to an understanding of the origin of life and the realization of de-novo life and ultimately, open-ended evolution.
Chapter 6
