Hitting Times of Some Critical Events in RNA Origins of Life

Caleb Deen Bastian, Hershel Rabitz

Research output: Contribution to journalArticlepeer-review

Abstract

Can a replicase be found in the vast sequence space by random drift? We partially answer this question through a proof-of-concept study of the times of occurrence (hitting times) of some critical events in the origins of life for low-dimensional RNA sequences using a mathematical model and stochastic simulation studies from Python software. We parameterize fitness and similarity landscapes for polymerases and study a replicating population of sequences (randomly) participating in template-directed polymerization. Under the ansatz of localization where sequence proximity correlates with spatial proximity of sequences, we find that, for a replicating population of sequences, the hitting and establishment of a high-fidelity replicator depends critically on the polymerase fitness and sequence (spatial) similarity landscapes and on sequence dimension. Probability of hitting is dominated by landscape curvature, whereas hitting time is dominated by sequence dimension. Surface chemistries, compartmentalization, and decay increase hitting times. Compartmentalization by vesicles reveals a trade-off between vesicle formation rate and replicative mass, suggesting that compartmentalization is necessary to ensure sufficient concentration of precursors. Metabolism is thought to be necessary to replication by supplying precursors of nucleobase synthesis. We suggest that the dynamics of the search for a high-fidelity replicase evolved mostly during the final period and, upon hitting, would have been followed by genomic adaptation of genes and to compartmentalization and metabolism, effecting degree-of-freedom gains of replication channel control over domain and state to ensure the fidelity and safe operations of the primordial genetic communication system of life.

Original languageEnglish (US)
Article number1419
JournalLife
Volume11
Issue number12
DOIs
StatePublished - Dec 2021

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Biochemistry, Genetics and Molecular Biology(all)
  • Space and Planetary Science
  • Palaeontology

Keywords

  • Fitness and similarity sequence landscapes
  • Global sensitivity analysis
  • High dimensional model representation
  • Hitting times
  • Measure-kernel-function
  • Ordinary differential equation
  • RNA world
  • Random counting measure
  • Stochastic simulation algorithm
  • Survival analysis

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