A roll of the dice: pathogen–host interaction and the evolution of disease susceptibility

The probability that a disease will manifest is highly variable. Susceptibility to disease is influenced by genetic background, environment and lifestyle choices. In this review, we put forward the premise that evolution of disease susceptibility may be partially influenced by the interaction of divergent pathogen DNA-binding proteins with variable binding sites in the host genome. The hypothesis put forward is derived from recent data obtained from work on the protozoan parasite, <i>Theileria annulata</i>, together with related evidence from viral and bacterial pathogens that have been postulated to modulate host epigenome architecture. The pathogen proteins highlighted have the potential to mimic functions of mammalian epigenome organisers linked to a range of disease syndromes. It is feasible, therefore, that the evolutionary relationship between pathogen and host impacts susceptibility to a range of conditions, such as autoimmune disorders and cancer, which are not directly linked to pathogen infection.