A stochastic model of nonenzymatic nucleic acid replication: "elongators" sequester replicators.

Area of Science:

• Origin of life studies
• Molecular evolution
• Chemical kinetics

Background:

• The origin of nucleic acid self-replication is a fundamental question in understanding life's beginnings.
• Existing models often do not account for competing reaction pathways like elongation.
• Template-directed nucleic acid replication is crucial for genetic inheritance.

Purpose of the Study:

• To develop a computational model for exploring conditions favoring nucleic acid template replication.
• To investigate the role of environmental cycling (e.g., temperature, tidal) in promoting replication.
• To identify necessary chemical or structural features for robust self-replication.

Main Methods:

• Development of a novel stochastic model for nucleic acid chemistry.
• Simulation of chemical experiments to test conditions for template replication.
• Analysis of reaction kinetics, specifically the competition between elongation and replication.

Main Results:

• The model revealed a strong tendency for nucleic acid elongation to outcompete template replication.
• Externally imposed cycles (tidal, temperature, monomer) did not overcome this elongation bias.
• Simulations showed that side-reactions, normally suppressed by polymerases, persisted under cycling conditions.

Conclusions:

• Simple cycling conditions are insufficient to drive nucleic acid self-replication due to competing elongation.
• Oligonucleotides capable of modulating the replication-to-elongation ratio are likely required.
• Early replicases may have incorporated restriction-like functions to favor replication over elongation.