Charting Evolutionary Paths and Alternate Outcomes of the Origin of Life

How did life originate on Earth? How might it have happened differently? The answers to these fundamental questions will inform efforts to develop useful synthetic organisms and empower the search for extraterrestrial life. The “RNA World” hypothesis posits that ribonucleic acid (RNA) once played the roles of both information carrier and catalyst in primitive living systems. In the transition from the RNA World to DNA-based heredity and catalysis by left-handed (L-)proteins, a likely essential step would have been the emergence of substrate-specific self-aminoacylating RNA enzymes (ribozymes) functioning in an early translation system. How these early self-replicating systems evolved toward modern cells, and what other outcomes might have been possible, are open questions. Evolution is conceptualized as a biased random walk through genetic space, in which each genotype is associated with a fitness (the “fitness landscape”). Mapping the fitness landscape for a given genetic element enables prediction of evolutionary paths. A recently developed method maps fitness landscapes for self-aminoacylating ribozymes by selection from a random library using prebiotically plausible activated amino acid analogs. In this work, we map the landscapes for self-aminoacylating ribozymes under variable environmental conditions and assess the effect of the environment on the topography and connectivity of fitness landscapes. We also evaluate the stereoselectivity of self-aminoacylating ribozymes to determine whether life’s transition to homochiral L-proteins was deterministic, or whether a right-handed (D-)protein world was possible. We find that a dynamic environment improves the connectivity of fitness landscapes, increasing the number of evolutionary paths available and enhancing evolution’s ability to optimize function. We also find that self-aminoacylating ribozymes can be either L- or D-selective, suggesting alternate possible outcomes for the chirality of life. These results represent incremental but meaningful contributions to human understanding of the emergence and evolution of primitive life