Relevance of Higher-Order Epistasis in Drug Resistance

• Published in: Molecular biology and evolution Vol. 38; no. 1; pp. 142 - 151
• Main Authors: Lozovsky, Elena R, Daniels, Rachel F, Heffernan, Gavin D, Jacobus, David P, Hartl, Daniel L
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.01.2021
• Subjects: Amino acids; Dihydrofolate reductase; Discoveries; Drug resistance; Drug therapy; Malaria; Plasmodium falciparum; Pyrimethamine; drug development; triazine antifolates; epistasis; adaptive topography; dihydrofolate reductase; Plasmodium falciparum

Abstract We studied five chemically distinct but related 1,3,5-triazine antifolates with regard to their effects on growth of a set of mutants in dihydrofolate reductase. The mutants comprise a combinatorially complete data set of all 16 possible combinations of four amino acid replacements associat...