Computer simulations of Template-Directed RNA Synthesis driven by temperature cycling in diverse sequence mixtures.

Area of Science:

• Origin of Life
• Molecular Evolution
• Computational Biology

Background:

• Template-directed RNA synthesis is a proposed mechanism for early life.
• The concept of a 'virtual circular genome' suggests mutually catalytic, overlapping RNA sequences.
• Understanding RNA replication fidelity is crucial for abiogenesis models.

Purpose of the Study:

• To simulate non-enzymatic RNA synthesis and assess sequence fidelity.
• To investigate the emergence and stability of virtual circular genomes.
• To evaluate the maintenance of functional RNA sequences in simulated protocell populations.

Main Methods:

• Computer simulations of RNA synthesis including primer extension, ligation, melting, and reannealing.
• Modeling of strand growth over multiple heating/cooling cycles.
• Analysis of sequence diversity, copying fidelity, and virtual circle formation under various conditions.

Main Results:

• RNA strands grow incrementally (1-2 nucleotides/cycle), leading to copying from multiple templates and diverse, non-exact sequences.
• Virtual circular genomes do not emerge naturally and require error-free replication and no new sequence input to persist.
• Functional sequences, even under selection in protocells, are not maintained due to sequence scrambling.

Conclusions:

• Non-enzymatic RNA synthesis inherently produces sequence diversity, challenging models of exact replication.
• The virtual circular genome hypothesis is unlikely to be a stable mechanism for early RNA replication.
• Sequence scrambling limits the maintenance of functional RNA molecules in early protocell systems.