epistasis

Kvitek DJ & Sherlock G 2011 Reciprocal sign epistasis between frequently experimentally evolved adaptive mutations causes a rugged fitness landscape. PLoS Genet 7:e1002056.

• adaptive mutations in two genes appear several times in different adaptive lineages
• they are selectively mutually exclusive due to reciprocal sign epistasis
• the genetic constraint between these two mutations causes a rugged fitness landscape, as both mutations occur multiple times during the evolution and are highly adaptive individually, while highly maladaptive in concert
• inter-genic interactions can act as barriers between adaptive solutions