Exobiology and Evolutionary Biology

Ribozyme Evolution by Transactivation

PI: Francis Schmidt

Objectives:
The RNA world model for prebiotic evolution posits the existence of a random library of RNAs that were selected for catalytic and other properties. The model requires (1) the population complexity of the RNA library must be sufficiently large to contain enough distinct species for selection of rare catalytic RNAs (2) Structural complexity so that individual RNA molecules are large enough for active catalysis. While relatively short RNAs can achieve population complexity, structural complexity is more problematic in short RNAs. De novo synthesis of structurally complex RNAs requires a highly processive polymerization mechanism, which has not been demonstrated in the RNA world.

Recombination of smaller RNAs could make larger RNAs, a process termed accretion. This is a three-step process of encounter, recombination and selection.The goal of this program is to determine the likelihood of the accretion mechanism under environmental conditions that are compatible with RNA structure and function. This determination requires kinetic and statistical descriptions of RNA encounter, recombination, and mutation in vitro.

Previous work showed that the first step is surprisingly likely. The current proposal is to (1) determine the likelihood of in vitro recombination between interacting RNAs (2) determine the frequency by which already recombined RNAs can be evolved into functional domains in composite RNAs.

Methods:
The system for study is the ribozyme RNase P RNA, for which the domain structure and enzymatic properties are well-known. Methods include RNA biochemical analysis and statistical analyses of the frequency of RNA events capable of carrying out the steps in accretion.

Significance to NASA goals:
This program directly relates to the goal of the Exobiology and Evolutionary Biology Program because it evaluates the ability of the RNA world “to serve as a precursor of metabolic and replicating systems on Earth and elsewhere.” Establishing likelihood parameters for the emergence of the RNA world will allow evaluation of other possible alternatives to Earth’s extant RNA-DNA-protein biochemical system. This will support the NASA objective of “exploring the Universe to understand its origin and structure” in support of the national goal to “explore the solar system and beyond.”