Polymorphism in the plant eukaryotic translation initiation factor 4E (eIF4E) and potyvirus genome-linked protein (VPg) determine, in many cases, the outcome of the confrontation between these two organisms: compatibility (i.e. infection of the plant by the virus) or incompatibility (i.e. resistance of the plant to the virus). The two interacting proteins eIF4E and VPg show strikingly similar evolution patterns. Most codon positions in their coding sequences are highly constrained for nonsynonymous substitutions but a small number shows evidence for positive selection. Several of these latter positions were shown to be functionally important, conferring resistance to the host or pathogenicity to the virus. Determining the mutational pathways involved in pepper eIF4E diversification revealed a link between an increase of the pepper resistance spectrum towards a panel of potyvirus species and an increase of durability of the resistance towards Potato virus Y. This relationship questions the interest of using more generally the spectrum of action of a plant resistance gene as a predictor of its durability potential.