The Cyclically Seasonal Drosophila subobscura Inversion O Originated From Fragile Genomic Sites and Relocated Immunity and Metabolic Genes

Chromosome inversions are important contributors to standing genetic variation in Drosophila subobscura. Presently, the species is experiencing a rapid replacement of high-latitude by low-latitude inversions associated with global warming. Yet not all low-latitude inversions are correlated with the ongoing warming trend. This is particularly unexpected in the case of O because it shows a regular seasonal cycle that peaks in summer and rose with a heatwave. The inconsistent behavior of O across components of the ambient temperature suggests that is causally more complex than simply due to temperature alone. In order to understand the dynamics of O, high-quality genomic data are needed to determine both the breakpoints and the genetic content. To fill this gap, here we generated a PacBio long read-based chromosome-scale genome assembly, from a highly homozygous line made isogenic for an O chromosome. Then we isolated the complete continuous sequence of O by conserved synteny analysis with the available reference genome. Main findings include the following: (i) the assembled O inversion stretches 9.936 Mb, containing > 1,000 annotated genes; (ii) O had a complex origin, involving multiple breaks associated with non-B DNA-forming motifs, formation of a microinversion, and ectopic repair in trans with the two homologous chromosomes; (iii) the O breakpoints carry a pre-inversion record of fragility, including a sequence insertion, and transposition with later inverted duplication of an Attacin immunity gene; and (iv) the O inversion relocated the major insulin signaling forkhead box subgroup O (foxo) gene in tight linkage with its antagonistic regulatory partner serine/threonine-protein kinase B (Akt1) and disrupted concerted evolution of the two inverted Attacin duplicates, reattaching them to dFOXO metabolic enhancers. Our findings suggest that O exerts antagonistic pleiotropic effects on reproduction and immunity, setting a framework to understand its relationship with climate change. Furthermore, they are relevant for fragility in genome rearrangement evolution and for current views on the contribution of breakage versus repair in shaping inversion-breakpoint junctions

Development of a high-quality annotated reference genome and evolutionary genomics analysis of chromosomal inversions in Drosophila subobscura

Drosophila subobscura és una espècie del grup obscura, un dels deu grups d'espècies coneguts del subgènere Sophophora, gènere Drosophila. Originàriament endèmica de la regió paleàrtica, l'espècie va colonitzar recentment Amèrica del Nord i del Sud. El sistema d'inversions cromosòmiques de D. subobscura representa un dels models més interessants per a investigar l'evolució d'aquesta mena de rearranjaments estructurals del genoma, ja que i) mostra nivells inusualment elevats de polimorfisme; i ii) s'ha detectat que està implicat en l'adaptació de l'espècie a l'escalfament global. La falta d'un genoma de referència per a l'espècie ha suposat un obstacle important per al seu estudi. Per a superar aquesta limitació hem abordat un assemblat de novo del genoma de D. subobscura utilitzant la tecnologia de "long-reads" PacBio. Els "long-reads" sense processar de PacBio es van assemblar utilitzant l'assemblador Canu. Per a avaluar la qualitat dels "contigs" i el "scaffolding" del genoma, es va desenvolupar un protocol semiautomàtic. A continuació, els "contigs" generats per Canu obtenint-se 186 "scaffolds" amb un N50 d'aproximadament 6Mb. L'assignació cromosòmica, l'ordre i l'orientació dels "scaffolds" van donar com a resultat sis pseudocromosomes, un per cadascun dels sis cromosomes de D. subobscura. Es van predir un total de 13.939 gens codificadors de proteïnes, i es va estimar que el 13% del genoma de l'espècie consisteix en seqüències repetitives. Finalment, es van determinar i van caracteritzar els punts de trencament de les inversions fixades entre D. subobscura i D. guanche. Els resultats obtinguts indiquen que l'evolució de l'estructura del genoma en D. subobscura és una conseqüència indirecta dels efectes de supressió de la recombinació de les inversions en el manteniment de conjunts d'al·lels adaptatius enfront del flux gènic D. subobscura està experimentant actualment un ràpid reemplaçament d'inversions de latituds altes per inversions de latituds baixes associat amb l'escalfament global. No totes les inversions de latituds baixes segueixen aquesta pauta, la qual cosa suggereix que les seves freqüències no depenen només de la temperatura. Un dels exemples més ben documentats és la inversió O7, la recerca de la qual s'ha vist obstaculitzada pel desconeixement de les seqüències dels seus punts de trencament genòmic. Per a abordar aquesta limitació, generem un assemblat del genoma a escala cromosòmica a partir d'una línia isogénica O3+4+7 utilitzant tecnologia de PacBio i seguint el protocol descrit anteriorment. Per a aïllar la seqüència completa d'O7 es va utilitzar una anàlisi de conservació de sintenia amb el genoma de referència. La inversió O7 es va originar mitjançant un mecanisme complex que va implicar múltiples trencaments associats amb motius d'ADN no-B, formació d'una microinversió i reparació ectòpica en trans amb els dos cromosomes homòlegs. Les nostres troballes recolzen que els punts de trencament de la inversió O7 tenien una història de fragilitat anterior a l'origen de la inversió, incloent-hi una inserció seguida d'una transposició amb una duplicació invertida d'un gen d'immunitat de la família de les atacinas. Respecte a alteracions gèniques, la inversió O7 va reubicar el principal gen del subgrup O (foxo) de senyalització de la insulina, acostant-lo al seu regulador antagònic, la serina/treonina-proteïna quinasa B (Akt1). A més, el seu punt de trencament distal va interrompre l'evolució concertada dels dos duplicats invertits de la atacina, connectant-los a elements potenciadors de dFOXO. Aquests descobriments suggereixen que O7 exerceix efectes pleiotrópicos antagònics sobre la reproducció i la immunitat, la qual cosa aporta un marc per a comprendre la seva relació amb el canvi climàtic. Les nostres troballes tenen implicacions generals per a les teories actuals sobre els mecanismes moleculars de formació de les inversions i el paper relatiu del trencament i la reparació en la formació dels seus punts de trencament.Drosophila subobscura es una especie del grupo obscura, uno de los diez grupos de especies conocidos del subgénero Sophophora, género Drosophila. Originariamente endémica de la región paleártica, la especie colonizó recientemente América del Norte y del Sur. El sistema de inversiones cromosómicas de D. subobscura representa uno de los modelos más interesantes para investigar la evolución de este tipo de rearreglos estructurales del genoma, ya que i) muestra niveles inusualmente elevados de polimorfismo y ii) se ha detectado que está implicado en la adaptación de la especie al calentamiento global. Sin embargo la falta de un genoma de referencia para la especie ha supuesto un obstáculo importante para su estudio. Para superar esta limitación hemos abordado un ensamblado de novo del genoma de D. subobscura utilizando la tecnología de "long-reads" PacBio. Los "long-reads" se ensamblaron utilizando el ensamblador Canu. Para evaluar la calidad de los "contigs" y el "scaffolding" del genoma, se desarrolló un protocolo semiautomático. Los "contigs" generados por Canu obteniéndose 186 "scaffolds" con un N50 de aproximadamente 6Mb. La asignación cromosómica, el orden y la orientación de los "scaffolds" dieron como resultado seis pseudocromosomas, uno por cada uno de los seis cromosomas de D. subobscura. Se predijeron un total de 13.939 genes codificadores de proteínas, y se estimó que el 13% del genoma de la especie consiste en secuencias repetitivas. Finalmente, se determinaron y caracterizaron los puntos de rotura de las inversiones fijadas entre D. subobscura y D. guanche. Los resultados obtenidos indican que la evolución de la estructura del genoma en D. subobscura es una consecuencia indirecta de los efectos de supresión de la recombinación de las inversiones en el mantenimiento de conjuntos de alelos adaptativos frente al flujo génico. D. subobscura está experimentando actualmente un rápido reemplazamiento de inversiones de latitudes altas por inversiones de latitudes bajas asociado con el calentamiento global. No todas las inversiones de latitudes bajas siguen esta pauta, lo que sugiere que sus frecuencias no dependen solo de la temperatura. Uno de los ejemplos mejor documentados es la inversión O7, cuya investigación se ha visto obstaculizada por el desconocimiento de las secuencias de sus puntos de rotura genómica. Para abordar esta limitación, generamos un ensamblado del genoma a escala cromosómica a partir de una línea isogénica O3+4+7 utilizando tecnología de PacBio. Para aislar la secuencia completa de O7 se utilizó un análisis de conservación de sintenia con el genoma de referencia. La inversión O7 se originó mediante un mecanismo complejo que implicó múltiples roturas asociadas con motivos de ADN no-B, formación de una microinversión y reparación ectópica en trans con los dos cromosomas homólogos. Nuestros hallazgos respaldan que los puntos de rotura de la inversión O7 tenían una historia de fragilidad anterior al origen de la inversión, incluyendo una inserción seguida de una transposición con una duplicación invertida de un gen de inmunidad de la familia de las atacinas. Con respecto a alteraciones génicas, la inversión O7 reubicó el principal gen del subgrupo O (foxo) de señalización de la insulina, acercándolo a su regulador antagónico, la serina/treonina-proteína quinasa B (Akt1). Además, su punto de rotura distal interrumpió la evolución concertada de los dos duplicados invertidos de la atacina, conectándolos a elementos potenciadores de dFOXO. Estos descubrimientos sugieren que O7 ejerce efectos pleiotrópicos antagónicos sobre la reproducción y la inmunidad, lo cual aporta un marco para comprender su relación con el cambio climático. Nuestros hallazgos tienen implicaciones generales para las teorías actuales sobre los mecanismos moleculares de formación de las inversiones y el papel relativo de la rotura y la reparación en la formación de sus puntos de rotura.Drosophila subobscura belongs to the obscura species group, which is one of the known ten species groups of the subgenus Sophophora of the genus Drosophila. Originally endemic from the Palearctic region, it has recently colonized North and South America. The chromosomal inversion system of D. subobscura represents one of the most interesting models to investigate the evolution of this type of genome rearrangement, because i) it shows extremely high levels of polymorphism, exhibiting inversions of all kinds regarding length and chromosomal location; and ii) it has been identified to be involved in the species' adaptation to contemporary global climate warming. The lack of a reference genome for the species has, however, stood as a major obstacle to its study. To overcome this limitation, here we have tackled a de novo assembly of the genome of D. subobscura using PacBio long-read technology. Raw PacBio reads were assembled using the Canu assembler. A semi-automated pipeline for assessing the quality of the contigs and scaffolding the genome has been developed that combined both synteny information from previously assembled genomes of D. melanogaster and D. pseudoobscura, and published data from 560 genetic markers derived from in situ hybridization experiments and genetic linkage analyses. Canu assembled contigs were then scaffolded resulting in 186 scaffolds with a N50 of approximately 6Mb. Chromosomal assignment, ordering and orientation of the scaffolds resulted in six pseudochromosomes, one for each of the six D. subobscura chromosomes. A total of 13,939 protein-coding genes were predicted, and 13% of the species genome was found to consist of repetitive sequences. Finally, the amounts of genome rearrangement between D. subobscura, D. guanche, D. melanogaster and D. pseudoobscura was assessed. The breakpoints of the fixed inversions between D. subobscura and D. guanche were determined and characterized. Here we illustrate that genome structure evolution in D. subobscura is driven indirectly, through the inversions' recombination-suppression effects in maintaining sets of adaptive alleles together in the face of gene flow. Presently, D. subobscura is experiencing a rapid replacement of high-latitude by low-latitude inversions associated with global warming. However, not all low-latitude inversions are correlated with the secular warming trend. The mixed behavior of O7 inversion across components of the ambient temperature suggests that it is driven by selective factors other than temperature alone. Research into this question has been hindered by lacking knowledge of the genomic breakpoint sequences of the inversion. To tackle this limitation, we generated a PacBio long read-based chromosome-scale genome assembly, from an O3+4+7 isogenic line. The complete continuous sequence of O7 was isolated using synteny analysis with the reference genome. Inversion O7 was shown to stretch 9.936 Mb, containing over 1,000 annotated genes. We illustrate that inversion O7 had a complex origin, involving multiple breaks associated with non-B DNA motifs, formation of a microinversion, and ectopic repair in trans with the two homologous chromosomes. Our findings support that inversion O7 breakpoints carry a pre-inversion record of fragility, including a sequence insertion, and transposition with later inverted duplication of an Attacin immunity gene. The O7 inversion was found to have relocated the major insulin signaling forkhead box subgroup O (foxo) gene bringing it in tight linkage with its antagonistic regulatory partner serine/threonine-protein kinase B (Akt1). Further, its distal breakpoint disrupted concerted evolution of the two inverted Attacin duplicates, reattaching them to dFOXO metabolic enhancers. We suggest that O7 exerts antagonistic pleiotropic effects on reproduction and immunity, setting a framework to understand its relationship with climate change. Our findings have general implications for current theories on the molecular mechanisms of formation of inversions and the contribution of breakage versus repair in shaping inversion-breakpoint junctions

ΕΝΕΡΓΕΙΑΙ ΤΗΣ ΠΡΟΠΡΑΝΟΛΟΛΗΣ ΚΑΙ ΟΞΠΡΕΝΟΛΟΛΗΣ ΕΠΙ ΤΩΝ ΛΕΙΩΝ ΜΥΙΚΩΝ ΙΝΩΝ ΕΝΤΕΡΟΥ ΙΝΔΟΧΟΙΡΟΥ ΚΑΙ ΜΗΤΡΑΣ ΕΠΙΜΥΟΣ.

ΕΚ ΤΩΝ ΑΝΩΤΕΡΩ ΠΡΟΚΥΠΤΕΙ ΟΤΙ ΩΣ ΚΑΙ ΕΙΣ ΤΗΝ ΠΕΡΙΠΤΩΣΙΝ ΤΗΣ ΠΡΟΝΑΙΘΑΛΟΛΗΣ^15 ΟΥΤΩ ΚΑΙ ΕΝΤΑΥΘΑ ΕΙΣ ΤΗΝ ΠΕΡΙΠΤΩΣΙΝ ΤΗΣ ΠΡΟΠΡΑΝΟΛΟΛΗΣ ΚΑΙ ΤΡΑΖΙΚΟΡΗΣ ΕΠΕΤΕΥΧΘΗΣΑΝ ΤΑ ΑΥΤΑ ΣΧΕΔΟΝ ΑΠΟΤΕΛΕΣΜΑΤΑ. ΕΝ ΤΟΥΤΟΙΣ ΠΟΣΟΤΙΚΩΣ ΑΙ ΔΥΟ ΑΥΤΑΙ ΟΥΣΙΑΙ ΔΡΟΥΝ ΑΣΘΕΝΕΣΤΕΡΟΝ Η Η ΠΡΟΝΑΙΘΑΛΟΛΗ^15, ΚΑΙ ΠΡΕΠΕΙ ΝΑ ΕΦΑΡΜΟΣΘΟΥΝ ΙΣΧΥΡΟΤΕΡΑΙ ΠΥΚΝΟΤΗΤΕΣ ΑΥΤΩΝ ΔΙΑ ΝΑ ΕΠΕΛΘΗ ΑΝΑΣΤΟΛΗ ΔΙΕΓΕΡΤΙΚΩΝ ΟΥΣΙΩΝ ΑΙΤΙΝΕΣ ΠΡΟΣΤΙΘΕΝΤΑΙ ΕΙΣ ΤΟ ΕΝΤΕΡΟΝ Η ΤΗΝ ΜΗΤΡΑΝ. ΤΑΥΤΑ ΠΑΝΤΑ ΒΕΒΑΙΩΣ ΔΕΝ ΣΗΜΑΙΝΟΥΝ ΟΤΙ Η ΑΝΑΣΤΑΛΤΙΚΗ ΕΝΕΡΓΕΙΑ ΤΩΝ ΟΥΣΙΩΝ ΤΟΥΤΩΝ ΕΠΙ ΤΩΝ Β - ΑΠΟΔΕΚΤΩΝ ΔΕΝ ΕΙΝΑΙ ΕΙΔΙΚΗ ΕΦ'ΟΣΟΝ ΕΠΕΚΤΕΙΝΕΤΑΙ ΚΑΙ ΕΙΣ ΑΛΛΟΥΣ ΑΠΟΔΕΚΤΑΣ. ΕΙΣ ΤΟΥΤΟ ΔΥΝΑΜΕΘΑ ΝΑ ΑΝΤΙΤΑΞΩΜΕΝ ΟΤΙ Η ΕΠΙ ΤΩΝ Β - ΑΠΟΔΕΚΤΩΝ ΑΝΑΣΤΑΛΤΙΚΗ ΕΝΕΡΓΕΙΑ ΕΚΔΗΛΟΥΤΑΙ ΚΑΙ ΟΤΑΝ ΑΙ ΔΙΕΓΕΡΤΙΚΑΙ ΑΥΤΑΙ ΟΥΣΙΑΙ ΤΩΝ Β - ΑΠΟΔΕΚΤΩΝ ΩΣ Η ΙΣΟΠΡΟΤΕΡΕΝΟΛΗ, ΠΡΟΣΤΕΘΟΥΝ ΕΙΣ ΑΠΕΙΡΟΕΛΑΧΙΣΤΑΣ ΠΟΣΟΤΗΤΑΣ ΩΣ 0,02 Γ /Κ.ΕΚ. ΕΝ ΑΛΛΟ ΖΗΤΗΜΑ ΤΟ ΟΠΟΙΟΝ ΠΡΟΚΥΠΤΕΙ ΕΚ ΤΩΝ ΕΡΕΥΝΩΝΤΟΥΤΩΝ, ΕΙΝΑΙ Η ΑΝΑΣΤΑΛΤΙΚΗ ΕΝΕΡΓΕΙΑ ΤΩΝ ΟΥΣΙΩΝ ΤΟΥΤΩΝ ΕΠΙ ΤΗΣ ΜΗΤΡΑΣ ΕΠΙΜΥΟΣΗΤΙΣ ΒΕΒΑΙΩΣ ΘΑ ΗΔΥΝΑΤΟ ΝΑ ΔΟΚΙΜΑΣΘΗ ΜΕΤΑ ΜΕΓΑΛΗΣ ΠΡΟΣΟΧΗΣ ΕΙΣ ΤΗΝ ΘΕΡΑΠΕΥΤΙΚΗΝ ΕΠΙ ΣΠΑΣΜΩΔΙΚΩΝ ΚΑΤΑΣΤΑΣΕΩΝ ΤΗΣ ΜΗΤΡΑΣ, ΠΡΑΓΜΑ ΟΠΕΡ ΒΕΒΑΙΩΣ ΔΕΝ ΓΝΩΡΙΖΟΜΕΝΕΑΝ ΕΧΗ ΔΟΚΙΜΑΣΘΗ. ΙΣΩΣ ΟΙ ΚΙΝΔΥΝΟΙ ΕΚ ΤΗΣ ΚΑΡΔΙΑΣ ΔΕΝ ΕΠΙΤΡΕΠΟΥΝ ΤΟΙΑΥΤΗΝ ΕΦΑΡΜΟΓΗΝ.THE RESULTS OF THE ABOVE INVESTIGATION DEMONSTRATE THAT, JUST AS IN THE CASE WITH PRONETHALOL, APPROXIMATELY THE SAME RESULTS WERE OBTAINED AS IN THE CASE WITH PROPRANOLOL AND TRASICOR. QUANTITATIVELY HOWEVER THESE TWO SUBSTANCES ARE LESS ACTIVE THAN PRONETHALOL AND STRONGER DENSITIES SHOULD BE ADMINISTERED IN ORDER TO BRING ABOUT INHIBITION OF THE STIMULATING SUBSTANCES WHICH ARE ADDED TO THE INTESTINE OR THE UTERUS. THIS DOES NOT MEAN HOWEVER THAT THE INHIBITORY ACTIVITY OF THESE SUBSTANCES ON THE BETA - RECEPTORS IS NOT SPECIFIC SINCE, ITIS EXTENDED TO OTHER RECEPTORS AS WELL. THIS INHIBITORY EFFECT HAS BEEN POSSIBLE TO DEMONSTRATE EVEN WHEN THE STIMULATING SUBSTANCES OF THE BETA - RECEPTORS, AS IN THE CASE OF ISOPROTERENOL, ARE ADDED IN VERY MINUTE QUANTITIES NAMELY 0.02 Γ/CC. THIS SHOWS THAT THE SPECIFICITY OF THE BETA - RECEPTORS TO THESESUBSTANCES IS VERY GREAT. ANOTHER MATTER WHICH RESULTS FROM THIS INVESTIGATION IS THE INHIBITORY ACTIVITY OF THESE SUBSTANCES ON THE UTERUS OF THE RAT WHICH GREAT CAUTION IN THERAPY OF CONTRACTILE CONDITIONS OF THE UTERUS. IT IS NOT KNOW HOWEVER THE ABOVE MATTER HAS BEEN DEALT WITH. PERHAPS THE DANGERS ARISING FROM THE HEART DO NOT PERMIT SUCH A PROCEDURE

Long-read based assembly and synteny analysis of a reference Drosophila subobscura genome reveals signatures of structural evolution driven by inversions recombination-suppression effects

Background: Drosophila subobscura has long been a central model in evolutionary genetics. Presently, its use is hindered by the lack of a reference genome. To bridge this gap, here we used PacBio long-read technology, together with the available wealth of genetic marker information, to assemble and annotate a high-quality nuclear and complete mitochondrial genome for the species. With the obtained assembly, we performed the first synteny analysis of genome structure evolution in the subobscura subgroup. Results: We generated a highly-contiguous ~ 129 Mb-long nuclear genome, consisting of six pseudochromosomes corresponding to the six chromosomes of a female haploid set, and a complete 15,764 bp-long mitogenome, and provide an account of their numbers and distributions of codifying and repetitive content. All 12 identified paracentric inversion differences in the subobscura subgroup would have originated by chromosomal breakage and repair, with some associated duplications, but no evidence of direct gene disruptions by the breakpoints. Between lineages, inversion fixation rates were 10 times higher in continental D. subobscura than in the two small oceanic-island endemics D. guanche and D. madeirensis. Within D. subobscura, we found contrasting ratios of chromosomal divergence to polymorphism between the A sex chromosome and the autosomes. Conclusions: We present the first high-quality, long-read sequencing of a D. subobscura genome. Our findings generally support genome structure evolution in this species being driven indirectly, through the inversions' recombination-suppression effects in maintaining sets of adaptive alleles together in the face of gene flow. The resources developed will serve to further establish the subobscura subgroup as model for comparative genomics and evolutionary indicator of global change

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

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

Glycosidase Hydrolase family 13 annotation.

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.</div