Genomic analysis of two phlebotomine sand fly vectors of Leishmania from the New and Old World

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. The leishmaniases are a group of neglected tropical diseases caused by protist parasites from the Genus Leishmania. Different Leishmania species present a wide clinical profile, ranging from mild, often self-resolving cutaneous lesions that can lead to protective immunity, to severe metastatic mucosal disease, to visceral disease that is ultimately fatal. Leishmania parasites are transmitted by the bites of sand flies, and as no approved human vaccine exists, available drugs are toxic and/or expensive and parasite resistance to them is emerging, new dual control strategies to combat these diseases must be developed, combining interventions on human infections and integrated sand fly population management. Effective vector control requires a comprehensive understanding of the biology of sand flies. To this end, we sequenced and annotated the genomes of two sand fly species that are important leishmaniasis vectors from the Old and New Worlds. These genomes allow us to better understand, at the genetic level, processes important in the vector biology of these species, such as finding hosts, blood-feeding, immunity, and detoxification. These genomic resources highlight the driving forces of evolution of two major Leishmania vectors and provide foundations for future research on how to better prevent leishmaniasis by control of the sand fly vectors

Genomic analysis of two phlebotomine sand fly vectors of Leishmania from the New and Old World.

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

Distribution plots of the pairwise <i>F</i>_<i>ST</i> between the different populations of <i>Lutzomyia longipalpis</i>.

Weighted FST values for 1kb non-overlapping windows were calculated across the genome for each population comparison. (TIF)</p

<i>Phlebotomus papatasi</i> population variant summary statistics.

Phlebotomus papatasi population variant summary statistics.</p

Admixture cross validation error.

Violin plot of the cross-validation error for each of 30 replicates for each K value. (A) Phlebotomus papatasi populations. (B) Lutzomyia longipalpis populations. (TIF)</p

<i>Lutzomyia longipalpis</i> population structure.

Inferred population structure of Lu. longipalpis individuals collected from Marajó (MAR; pink), Lapinha (LAP; blue), from Jacobina (JAC; red), and Sobral, including Sobral 1S (S1S; orange) and 16 Sobral 2S (S2S; green). (A) Rooted neighbor joining (NJ) radial tree. We included both N. intermedia (INT; yellow) and M. migonei (MIG; purple) and used M. migonei to root the trees. Bootstrap values represent the percentage of 1,000 replicates. (B) Principal component analysis (PCA). Individuals were plotted according to their coordinates on the first two principal components (PC1 and PC2). (C) Admixture analysis. Ancestry proportions for Admixture models from K = 2 to K = 7 ancestral populations. Each individual is represented by a thin vertical line, partitioned into K coloured segments representing the individual’s estimated membership fractions to the K clusters. These data are the average of the major q-matrix clusters derived by CLUMPAK analysis.</p

Parameter values of male copulatory songs from <i>Lutzomyia longipalpis</i> from Araci and Olindina.

Parameter values of male copulatory songs from Lutzomyia longipalpis from Araci and Olindina.</p

Mitogen activated protein kinase family annotation.

Mitogen activated protein kinase family annotation.</p

<i>Lutzomyia longipalpis</i> genes within differentiation islands.

Lutzomyia longipalpis genes within differentiation islands.</p