Figure 6:

Schematic of epistatic interactions between two variants. A. A newly emerged variant (A>a) in the population might be harmful, neutral, or advantageous. Beneficial new variants are favored by natural selection and become fixed in the population very rapidly. In contrast, highly detrimental variants are removed by natural selection or persist in the population only at low frequencies. B. Under the epistatic interactions model, both A>a and B>b mutations are slightly deleterious. A virus with either an Ab or aB genotype has reduced fitness relative to the AB genotype. The virus with the ab genotype has a normal or even higher fitness. Thus, epistatic interactions can cause linkages between variants at the two sites to be maintained during viral evolution.