The Scope of Selection

Abstract

We have estimated the maximal size for an RNA motif recoverable from selection-amplification for new RNA activities, under conditions that span those in present laboratory use. The number of sequence pieces from which an active site is folded (the modularity) is a crucial variable. Routine laboratory experiments might isolate RNAs of modularity 4 containing 33 specified nucleotides. The probability of recovering shorter motifs increases rapidly, but the likely maximal motif size declines 1.66 nucleotides per 10-fold decrease in experimental scale. In such experiments, randomized tracts of 80-120 nucleotides extract most of the benefit of longer initially randomized pools. The same methods also permit extrapolation to conditions more plausible during the initiation of an RNA world. Under these conditions, active RNAs were likely highly modular, even more so than in modern experiments. Strikingly, several lines of evidence converge on the conclusion that 15 to 35-mer active sites would be the working material for an early RNA world. If initiation of an RNA world is synonymous with emergence of active structures from randomized sequences (the Axiom of Origin), populations containing only zeptomoles of RNA (hundreds to hundreds of thousands of molecules) might yield RNAs at the lower end of this size range. This makes the RNA world much more accessible than previously suspected.