compensatory evolution

Casci T 2010 Concealed connections. Nat Rev Genet 11:818.

• all compensatory mutations were located at physically distant sites from F37L
• suggesting that the search for compensatory mutations can also highlight new structure–function relationships

• the fitness cost of any mutation is tiny, suggesting that cryptic epistasis arises by neutral evolution
• the temporal order in which mutations occurred in the lineage leading to E. coli and P. aeruginosa supports the idea that the F37L-interacting mutations were built up by a 'nearly neutral' process
• a series of slightly deleterious alleles would have been fixed by random drift, until the fixation of a fully compensatory mutation by positive selection

• many protein functions are locked in place by rampant epistasis
• neutral mutations can provide rare opportunities for new functions to evolve