Human settlement drives population divergence of Leishmania guyanensis at the sylvatic-anthropogenic interface

The Amazon is the largest tropical rainforest in the world, and is an important interface between natural rainforest and anthropogenic environments. In the central Amazon region, Leishmania guyanensis is a common agent of cutaneous leishmaniasis (CL), a disfiguring vector-borne disease that circulates between wild mammalian reservoirs and sandfly vectors in sylvatic cycles. People become infected when they interact or disturb this cycle. At present, little is known about the adaptation of Leishmania parasites at the interface between sylvatic and anthropogenic environments. Here, to characterize CL in a transition zone, we conducted a population genomic analysis of 77 Leishmania isolates from human patients living in Manauss outskirts or in highways adjacent to the Brazilian Amazon rainforest. We discovered two L. guyanensis populations; an ancestral sylvatic population occurring in densely forested areas far from the city and a derived population, occurring in areas with lower forest cover closer to the city (the city-proximal population). The genomic divergence between these populations indicates that their separation occurred relatively recently, consistent with human-driven development of a new transmission cycle for CL in the Manaus region. The lack of recent gene flow between these populations indicates that the newer city-proximal population has established a transmission cycle that operates independently from ancestral sylvatic transmission. This provides a striking example of the adaptation of disease transmission to an environment that has been altered by human activity. Significance StatementEmerging infectious diseases often arise at the interface between natural and human-modified environments. One of these important interfaces is the Amazon, the largest rainforest in the world. We analyzed the population genomics of Leishmania guyanensis, the agent of cutaneous leishmaniasis in the Amazon, typically transmitted in sylvatic cycles. Our findings reveal a recent emergence of a L. guyanensis population associated with anthropogenic environment alterations, which is genetically distinct from the ancestral sylvatic lineage. This newly adapted population highlights how landscape change and urban expansion may drive the evolution and emergence of protozoan vector-borne pathogens at the rainforest-urban interface.