Phlebotomine sand flies are of global significance as important vectors of human disease, transmitting bacterial, viral, and protozoan pathogens, including the kinetoplastid parasites of the genus Leishmania, the causative agents of devastating diseases collectively termed leishmaniasis. More than 40 pathogenic Leishmania species are transmitted to humans by approximately 35 sand fly species in 98 countries with hundreds of millions of people at risk around the world. No approved efficacious vaccine exists for leishmaniasis and available therapeutic drugs are either toxic and/or expensive, or the parasites are becoming resistant to the more recently developed drugs. Therefore, sand fly and/or reservoir control are currently the most effective strategies to break transmission. To better understand the biology of sand flies, including the mechanisms involved in their vectorial capacity, insecticide resistance, and population structures we sequenced the genomes of two geographically widespread and important sand fly vector species: Phlebotomus papatasi, a vector of Leishmania parasites that cause cutaneous leishmaniasis, (distributed in Europe, the Middle East and North Africa) and Lutzomyia longipalpis, a vector of Leishmania parasites that cause visceral leishmaniasis (distributed across Central and South America). We categorized and curated genes involved in processes important to their roles as disease vectors, including chemosensation, blood feeding, circadian rhythm, immunity, and detoxification, as well as mobile genetic elements. We also defined gene orthology and observed micro-synteny among the genomes. Finally, we present the genetic diversity and population structure of these species in their respective geographical areas. These genomes will be a foundation on which to base future efforts to prevent vector-borne transmission of Leishmania parasites.

CNRS UPR9022 Institut de Biologie Moléculaire et Cellulaire and Faculté des Sciences de la Vie Université de Strasbourg Strasbourg France

Department of Animal Sciences Department of Surgery Institute for Data Science and Informatics University of Missouri Columbia Missouri United States of America

Department of Biochemistry and Immunology Instituto de Ciências Biológicas Universidade Federal de Minas Gerais Belo Horizonte Brazil

Department of Biological Sciences California State Polytechnic University Pomona California United States of America

Department of Biological Sciences University of Cincinnati Cincinnati Ohio United States of America

Department of Biology and Center for Biological Clocks Research Texas A and M University College Station Texas United States of America

Department of Biology University of Crete Voutes University Campus Heraklion Greece

Department of Chemical and Biomolecular Engineering University of Notre Dame Notre Dame Indiana United States of America

Department of Ecology and Evolution and Swiss Institute of Bioinformatics University of Lausanne Lausanne Switzerland

Department of Electrical Engineering and Computer Science Milwaukee School of Engineering Milwaukee Wisconsin United States of America

Department of Electrical Engineering and Computer Science University of Tennessee Knoxville Tennessee United States of America

Department of Entomology University of Kentucky Lexington Kentucky United States of America

Department of Life Sciences Faculty of Science and Technology Al Quds University Jerusalem Palestine

Department of Microbiology Instituto de Ciências Biológicas Universidade Federal de Minas Gerais Belo Horizonte Brazil

Department of Neuroscience Perelman School of Medicine University of Pennsylvania Philadelphia Pennsylvania United States of America

Department of Parasitology Faculty of Science Charles University Prague Czech Republic

Dept Ciencias Biológicas and Dept Ciencias Básicas Médicas Universidad Icesi Cali Colombia

Discovery Partners Institute University of Illinois Chicago Chicago Illinois United States of America

Division of Biological Sciences Section of Cell and Developmental Biology University of California San Diego California United States of America

Division of Biomedical and Life Sciences Faculty of Health and Medicine Lancaster University Lancaster United Kingdom

Donald Danforth Plant Science Center Olivette Missouri United States of America

Eck Institute for Global Health Department of Biological Sciences University of Notre dame Notre Dame Indiana United States of America

F Edward Hebert School of Medicine Department of Preventive Medicine and Biostatistics Uniformed Services University of the Health Sciences Bethesda Maryland United States of America

Fralin Life Science Institute and Department of Biochemistry Virginia Tech Blacksburg Virginia United States of America

Genomic Sciences and Precision Medicine Center Medical College of Wisconsin Milwaukee Wisconsin United States of America

Genomics Group Bioinformatics and Evolutionary Biology Lab Department of Genetics and Microbiology Autonomous University of Barcelona Barcelona Spain

Human Genome Sequencing Center Baylor College of Medicine Houston Texas United States of America

Institute of Integrative Biology The University of Liverpool Liverpool United Kingdom

Instituto Oswaldo Cruz Fiocruz Rio de Janeiro Brazil

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

Laboratório de Bioquímica e Fisiologia de Insetos IOC FIOCRUZ Rio de Janeiro Brazil

Laboratório de Doenças Parasitárias Instituto Oswaldo Cruz Rio de Janeiro Brazil

Laboratório de Fisiologia de Insetos Hematófagos Universidade Federal de Minas Gerais Instituto de Ciencias Biológicas Departamento de Parasitologia Pampulha Belo Horizonte Brazil

Laboratório de Imunoparasitologia CPqGM Fundação Oswaldo Cruz Bahia Brazil

Laboratorio de Insectos Sociales Instituto de Fisiología Biología Molecular y Neurociencias Universidad de Buenos Aires CONICET Buenos Aires Argentina

Laboratório de Transmissores de Hematozoários IOC FIOCRUZ Rio de Janeiro Brazil

Laboratory Interdisciplinar em Vigilancia Entomologia em Diptera e Hemiptera Fiocruz Rio de Janeiro Brazil

Laboratory of Cell Biology Development and Genetics Department of Biochemistry University of Oxford Oxford United Kingdom

Laboratory of Medical Entomology René Rachou Institute FIOCRUZ Belo Horizonte Brazil

McDonnell Genome Institute Washington University School of Medicine St Louis Missouri United States of America

Medical Entomology Branch Dept Microbiology Bundeswehr Hospital Hamburg Germany

Medical Zoology Branch Dept Microbiology Central Bundeswehr Hospital Koblenz Germany

Molecular Entomology Lab Institute of Molecular Biology and Biotechnology Foundation for Research and Technology Hellas Heraklion Greece

Pesticide Science Lab Department of Crop Science Agricultural University of Athens Athens Greece

School of Applied Mathematics Getulio Vargas Foundation Rio de Janeiro Brazil

School of Biological and Environmental Sciences Liverpool John Moores University Liverpool United Kingdom

Universidade Federal do Rio de Janeiro Instituto de Biologia Rio de Janeiro Brazil

USDA ARS Knipling Bushland U S Livestock Insects Research Laboratory and Veterinary Pest Genomics Center Kerrville Texas United States of America

Vector Biology Department Liverpool School of Tropical Medicine Liverpool United Kingdom

Vector Ecology Unit Institut Pasteur de Tunis Tunis Tunisia

Vector Molecular Biology Section Laboratory of Malaria and Vector Research National Institute of Allergy and Infectious Diseases National Institutes of Health Rockville Maryland United States of America

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Stability and suitability of housekeeping genes in phlebotomine sand flies

Comparative Genomics Uncovers the Evolutionary Dynamics of Detoxification and Insecticide Target Genes Across 11 Phlebotomine Sand Flies

Rhabdoviral Endogenous Sequences Identified in the Leishmaniasis Vector Lutzomyia longipalpis Are Widespread in Sandflies from South America