ИСТИНА

Intragenic compensation is a specific case of positive epista- sis in which a neutral missense mutation alleviates effect of a deleterious mutation in the same protein. Such compensatory (trailing) or permissive (preceding) mutations facilitate protein evolution: since most mutations are deleterious, without compensation all sequences would be extremely conserved. Understanding intragenic compensation mechanisms is impor- tant both from practical point of view and to understand the fundamen- tal basis of protein biophysics and evolution. Deep mutational scanning enables experimental studies of functional effects of thousands of sin- gle and double mutations in proteins. We conducted a meta-analysis of eight DMS datasets with quantified functional effects of single and dou- ble mutations, described rates and patterns of intragenic compensation and reviewed existing limitations of current data