98-03-006
Complete Suboptimal Folding of RNA
and the Stability of Secondary Structures
An algorithm is presented for generating rigorously all
suboptimal secondary structures between the minimum free energy and an
arbitrary upper limit. The algorithm performs particularly well in the
vicinity of the minimum free energy. This enables the efficient
approximation of statistical quantities, such as the partition
function or measures for structural diversity. The density of states
at low energies and its associated structures are crucial in assessing
from a thermodynamic point of view how well defined the ground
state is. We demonstrate this by exploring the role of base
modification in tRNA secondary structures, both at the level of
individual sequences from E. coli and by comparing
artificially generated ensembles of modified and unmodified sequences
with the same tRNA structure. The two major conclusions are that (1)
base modification considerably sharpens the definition of the ground
state structure by constraining energetically adjacent structures to
be similar to the ground state, and (2) sequences whose ground state
structure is thermodynamically well defined show a significant
tendency to buffer single point mutations. This can have evolutionary
implications, since selection pressure to improve the definition of
ground states with biological function may result in increased
neutrality.
Keywords: RNA secondary structure, suboptimal folding, density of states,
tRNA, modified bases, thermodynamic stability of structure, mutational
buffering, neutrality, dynamic programming