The Origin of Life in the Laboratory

A longstanding research goal has been to construct an artificial genetic system that can undergo self-sustained replication and evolution, brought about by enzymatic machinery that is part of the system being replicated. One way to realize this goal, as first articulated by Francis Crick in 1968, would be for an RNA enzyme to catalyze the replication of RNA molecules, including the RNA enzyme itself. This has recently been achieved in a cross-catalytic system involving two RNA enzymes that catalyze each other's synthesis from a total of four component substrates. The cross-replicating RNA enzymes undergo self-sustained exponential amplification at constant temperature and in the absence of proteins or other biological materials. Amplification occurs with a doubling time of about one hour, and can be continued indefinitely. Small populations of cross-replicating RNA enzymes were constructed and allowed to compete for limited resources within a common reaction mixture. The molecules reproduced with high fidelity, but occasionally gave rise to recombinants that also could replicate. Over the course of many "generations" of selective amplification, novel variants arose and grew to dominate the population based on their enhanced fitness under the chosen reaction conditions. The system is not yet capable of open-ended Darwinian evolution resulting in the emergence of novel function. However, self-replication can be made dependent on the execution of other RNA-based functions, with the replication rate being determined by how well that other function is executed. It is likely that systems of this kind will eventually be capable of self-sustained Darwinian evolution, something many regard as being synonymous with the origin of life.