Recombination and purifying and balancing selection determine the evolution of major antigenic protein 1 (map 1) family genes in Ehrlichia ruminantium

Abstract

Heartwater is an economically important disease of ruminants caused by the tick-borne bacterium Ehrlichia ruminantium. The disease is present throughout sub-Saharan Africa as well as on several islands in the Caribbean, where it poses a risk of spreading onto the American mainland. The dominant immune response of infected animals is directed against the variable outer membrane proteins of E. ruminantium encoded by a polymorphic multigene family. Here, we examined the full-length sequence of the major antigenic protein 1 (map1) family genes in multiple E. ruminantium isolates from different African countries and the Caribbean, collected at different time points to infer the possible role of recombination breakpoint and natural selection. A high level of recombination was found particularly in map1 and map1–2. Evidence of strong negative purifying selection in map1 and balancing selection to maintain genetic variation across these samples from geographically distinct countries suggests host–pathogen co-evolution. This co-evolution between the host and pathogen results in balancing selection by maintaining genetic diversity that could be explained by the demographic history of long-term pathogen pressure. This signifies the adaptive role and the molecular evolutionary forces underpinning E. ruminantium map1 multigene family antigenicity.