Leishmania infantum causes visceral leishmaniasis, a deadly vector-borne disease introduced to the Americas during the colonial era. This non-native trypanosomatid parasite has since established widespread transmission cycles using alternative vectors, and human infection has become a significant concern to public health, especially in Brazil. A multi-kilobase deletion was recently detected in Brazilian L. infantum genomes and is suggested to reduce susceptibility to the anti-leishmanial drug miltefosine. We show that deletion-carrying strains occur in at least 15 Brazilian states and describe diversity patterns suggesting that these derive from common ancestral mutants rather than from recurrent independent mutation events. We also show that the deleted locus and associated enzymatic activity is restored by hybridization with non-deletion type strains. Genetic exchange appears common in areas of secondary contact but also among closely related parasites. We examine demographic and ecological scenarios underlying this complex L. infantum population structure and discuss implications for disease control.

Department of Cell and Molecular Biology Science for Life Laboratory Karolinska Institutet Biomedicum 9C 171 77 Stockholm Sweden

Department of Parasites and Insect Vectors Institut Pasteur INSERM U1201 Unité de Parasitology moléculaire et Signalisation 75015 Paris France

Faculty of Science Department of Parasitology Charles University 128 44 Prague Czech Republic

Institut Pasteur Bioinformatics and Biostatistics Hub C3BI USR 3756 IP CNRS 75015 Paris France

Instituto de Bioquímica Médica Leopoldo de Meis 21941 590 Rio de Janeiro RJ Brazil

Laboratório de Biologia Molecular de Parasitas e Vetores Instituto Oswaldo Cruz 21040 365 Rio de Janeiro Brazil

Laboratório de Biologia Molecular e Doenças Endêmicas Instituto Oswaldo Cruz Fiocruz 21040 365 Rio de Janeiro RJ Brazil

Laboratório de Pesquisa em Leishmaniose Instituto Oswaldo Cruz FIOCRUZ 21040 365 Rio de Janeiro Brazil

School of Life Sciences Institute of Biodiversity Animal Health and Comparative Medicine University of Glasgow G12 8QQ Glasgow UK

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Gene deletion as a possible strategy adopted by New World Leishmania infantum to maximize geographic dispersion

Comparative genomics of Leishmania donovani progeny from genetic crosses in two sand fly species and impact on the diversity of diagnostic and vaccine candidates