RNA FOLDING IN DROSOPHILA SHOWS A DISTANCE EFFECT FOR COMPENSATORY FITNESS INTERACTIONS

Phylogenetic-comparative analysis was used to construct a secondary st ructure of Adh precursor messenger RNA (pre-mRNA) in Drosophila. The a nalysis revealed that the rate of coevolution of base-pairing residues decreases with their physical distance. This result is in qualitative agreement with a model of compensatory fitness interactions which ass umes that mutations are individually deleterious but become harmless ( neutral) in appropriate combinations. This model predicts that coupled mutations can become fixed in a population under mutation pressure an d random genetic drift, when the mutations are closely linked. However , the rate of joint fixation drops as distance between sites increases and recombination breaks up favorable combinations. RNA secondary str ucture was also used to interpret patterns of linkage disequilibrium a t Adh.