STABILITY OF REPLICATIVE FORM AND FITNESS AMONG RNA VARIANTS TRANSCRIBED BY Q-BETA REPLICASE

Stability in the replicative form of RNA molecules transcribed by Q be ta replicase was demonstrated to provide a sequence-dependent indicato r of their fitness. This follows from the finding that replication rat es reported for 17 RNA species (genome length, 77-370 nucleotides) cor relate with the self-interaction free energy of these self-annealed st rands. Formation of double-stranded molecules during replication conve rsely decreased with self-interaction free energy. H-bond formation be tween self-complementary segments of folded RNA molecules plainly prod uces a potential energy barrier opposing the transition to a double-st randed, non-replicating form. Melting point temperature and resistance of RNA synthesis to elevated salt levels among three variants also in creased with strand configuration free energy. Genome-based estimates of fitness in other self-replicating RNA species were therefore possib le. Once a link between the kinetic parameters of replication and base sequence of these RNA species is adequately established, estimates of fitness can be dissociated from survival rates following evolution, a nd Darwin's fundamental precept, 'survival of the fittest', could be a ppraised as an experimentally testable hypothesis.