Thermodynamic and Kinetic Sequence Selection in Enzyme-Free Polymer Self-Assembly inside a Non-equilibrium RNA...

Area of Science:

• Origin of Life Research
• Prebiotic Chemistry
• Molecular Evolution

Background:

• The RNA world hypothesis proposes RNA's dual role in early life as genetic material and catalyst.
• The origin of catalytic RNA molecules and the transition from a pre-RNA to an RNA world remain key unanswered questions.
• Understanding the collective evolution of short oligonucleotides into longer, functional RNA is crucial.

Purpose of the Study:

• To investigate the sequence-dependent self-assembly of polymers from short building blocks via templated ligation.
• To model the dynamics of RNA molecule formation in a non-equilibrium 'RNA reactor' with periodic temperature changes.
• To identify factors driving the transition from a pre-RNA to an RNA world, focusing on sequence selection mechanisms.

Main Methods:

• Development of a stochastic model incorporating sequence-dependent thermodynamic and kinetic effects of templated ligation.
• Simulation of an 'RNA reactor' system with chemical activation and periodic temperature fluctuations.
• Analysis of strand growth, cleavage by hydrolysis, and the resulting non-equilibrium stationary state of the oligomer pool.

Main Results:

• Sequence context significantly influences ligation probability through both thermodynamic stability and kinetic stalling.
• Kinetic stalling, caused by non-complementary base pairs, is identified as a critical factor for self-enhancing sequence selection.
• The model demonstrates how kinetic stalling leads to self-amplification cascades, reducing the diversity of occupied sequence space.

Conclusions:

• Kinetic stalling in templated ligation is a key mechanism facilitating the emergence of longer RNA molecules and sequence selection.
• The simulated 'RNA reactor' environment supports the development of a non-equilibrium stationary state with specific length and sequence distributions.
• Symmetry breaking, driven by kinetic stalling, plays a significant role in the transition from a pre-RNA to an RNA world.