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PNAS

Contingency and entrenchment in protein evolution under purifying selection [Evolution]

P. Shah, D. M. McCandlish, J. B. Plotkin.
The phenotypic effect of an allele at one genetic site may depend on alleles at other sites, a phenomenon known as epistasis. Epistasis can profoundly influence the process of evolution in populations and shape the patterns of protein divergence across species. Whereas epistasis between adaptive substitutions has been studied extensively,...