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Rio Ondo

Rio Ondo

Affiliation

University of Chicago

Supervisors

  • Jack Szostak (University of Chicago)
  • Arvind Murugan (University of Chicago)

Short bio

I am a PhD student in molecular engineering at the University of Chicago. I received my undergraduate degree in physics from the University of California, Santa Barbara. My research asks how accurate genetic replication could have emerged before the molecular machinery that makes it possible. During the Enrico Fermi Fellowship, I will use theory and experiment to test whether simply replicating faster can, on its own, generate the accuracy needed for life to begin.

Evolution of prebiotic proofreading

Life today relies on a carefully organized flow of genetic information: DNA stores instructions, RNA carries those instructions, and proteins perform most of the chemical work in cells. However, this division of labor raises a fundamental question: how could such an interdependent system have arisen at the origin of life? One prominent model addressing this problem is the RNA world hypothesis, in which RNA molecules both stored genetic information and catalyzed chemical reactions.

For such a system to evolve, RNA molecules would need to replicate themselves. This raises a major problem: copying genetic information is error-prone. If too many mistakes occur, useful information is quickly lost, preventing evolution from sustaining complex molecules. Modern cells solve this problem using sophisticated enzymes that correct copying errors, but these systems appear far too complex to have existed at the very beginning of life.

Interestingly, the basic principle behind error correction may be much simpler than it seems. When an incorrect building block is added during copying, it often slows down the process because the mismatch makes further extension difficult. This creates an opportunity for systems that remove mistakes and resume copying to grow faster overall. In this way, error correction might have first emerged not to improve accuracy directly, but simply as a way to replicate more efficiently. Thus, error correction can emerge naturally from the combination of stalling at mistakes and occasional reversal, without the need for complex machinery.

This project explores whether such a mechanism could operate in simple RNA systems. In laboratory experiments, a large pool of random RNA molecules is subjected to selection for fast replication. Some molecules may achieve faster growth by removing errors and restarting replication, effectively performing a simple form of proofreading.

At the same time, theoretical simulations help predict how factors such as mutation rates and the strength of replication stalling influence evolutionary outcomes. The combination of theory and experiment provides a framework for understanding how early molecular systems could have improved replication accuracy before the emergence of modern enzymes, offering new insight into how life may have first evolved.

Rio Ondo's project image