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Araujo, R. N.

Publications and source records attributed to Araujo, R. N..

3 recordsLinked to original sources

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 devastating kinetoplastid parasites of the genus Leishmania, the causative agents of 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. As no approved efficacious vaccine exists, available drugs are expensive and/or toxic, and resistance is emerging, management of sand fly populations to break transmission is currently the most effective disease control strategy. 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 of the most important sand fly species: Phlebotomus papatasi, a cutaneous leishmaniasis vector, (distributed in the Middle East and North Africa) and Lutzomyia longipalpis, a visceral leishmaniasis vector (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. Author SummaryThe 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 vaccine exists, available drugs are toxic and/or expensive and resistance 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 good 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.

genomics↗

The Drosophila fertility factor kl-3 is linked to the Y-chromosome of the vector of Chagas’ disease Triatoma infestans (Hemiptera: Reduviidae) and is essential for male fertility

In many insects, the Y chromosome plays a key role in sexual determination and male fertility. The Chagas disease vector Triatoma infestans has 22 autosomal chromosomes and a pair of XY sex chromosomes. However, the knowledge on the Y chromosome of this species, its genetic content or its biological function, is very poor. Due to repetitive DNA, Y chromosome sequences are poorly assembled in genome projects, hindering structural and functional studies on Y-linked genes. Our group has developed many of the bioinformatic tools to identify Y-linked sequences in assembled genomes. Here, we describe the identification of a {gamma}-dynein heavy chain linked to the Y-chromosome of T. infestans. This protein is orthologous to the Drosophila melanogaster Y-linked gene kl-3. In D. melanogaster, dyneins of the Y chromosome are known as male fertility factors and their deletion causes male infertility. We performed knockdown of the kl-3 expression to ascertain its function in T. infestans. Our results showed that injection of dsKL3 reduced, significantly, the fertility of T. infestans males (p<0.01). The mean number of eggs laid by the control group was 35.64 eggs/couple while the kl-3 knockdown group was of 11.82 eggs/couple (five couples did not lay any eggs). Differences in eclosion rate was even more significant, with a hatching mean rate of 16.85{+/-}10.03 and 1.69{+/-}3.58 (p<0.001) for the control and the silenced groups respectively. Our results suggest that kl-3 maintains its functional role as essential for male fertility in T. infestans. Hence, it seems that the Y-chromosome of T. infestans has a key role in male fertility. This is the first report of a kl-3 orthologue linked to the Y chromosome of an insect species outside the diptera clade. In addition to the first report of a Y-linked gene in T. infestans with a role for male fertility, this finding is of great relevance for the study of the evolution of Y chromosomes and further studies that could lead to novel approaches in insect control.

genomics↗

Analysis of the testis transcriptome of the Chagas’ disease vector Rhodnius prolixus

Rhodnius prolixus is amongst the most important vectors of Trypanosoma cruzi in the Americas, putting thousands of people at risk of contracting Chagas Disease. This insect is also one of the most important models in insect physiology, especially regarding the blood-feeding process. However, studies on R. prolixus genetics lagged, and our understanding on the regulation of gene expression is incipient. Transcriptomes have the power to study the expression of thousands of genes in a single experiment. A comprehensive R. prolixus transcriptome was performed in 2014, sequencing RNA from different tissues (anterior gut, midgut, posterior gut, rectum, ovaries, fat body, maphigian tubules, and testicles). However, on that occasion, only the gut transcriptome was deeply analysed. Here we evaluated the results of the testicles transcriptome of R. prolixus with the objective to find and understand genes that could have an important role in male reproduction. We found, that from the 25,673 transcripts assembled in the whole transcriptome, 5,365 have a testicle specific expression pattern. As expected, amongst the most abundant families of transcripts, are those related to spermatogenesis and male fertility, such as myosins, actins, and dyneins. To our surprise, lipocalins, serine protease inhibitors (serpins), and lysozymes also were highly abundant in testicles. The role of these classes of genes are well known in other tissues, such as salivary glands and gut, but very little is known on their role in male reproduction (and we proposed here a few hypothesis that could be tested to address the role of these genes in male fertility). It would be interesting to study further the role of these genes on R. prolixus male fertility. Finally, as a reflection of the lack of knowledge on triatomine genetics, we found that almost half of the transcripts in R. prolixus testicles have no similarities to any other genes on reference databases. Our study shows that we still have a lot to know and to understand about reproduction in triatomine, especially in males. Besides the large number of genes without described function (possibly novel genes), there are those in which the function is known for other tissues, and we can only guess, at best, the role and importance of such genes for triatomine male fertility. Author SummaryThe understanding of the biology of insects vectors of parasitic diseases is key to the development of strategies of public health. For decades, the studies on the biology of male insects vectors of diseases was neglected, since in many cases female insects are those with relevant role in the spread of diseases. With the development of genomics, large scale studies to compare differential gene expression (transcriptomics) among different tissues, developmental stages, and sex became accessible. In this study, we looked at the physiology of the male reproductive organs of the vector of Chagas disease Rhodnius prolixus. This is a first glimpse, from a perspective of genes differentially expressed in male gonads, in such insects. We also performed an effort to link all identified genes with the insect genome published in 2015. We found ~14,000 genes expressed in the testicles, from which 5,635 genes are expressed exclusively in male reproductive organs. From the ~14,000 genes, we were able to attribute putative biological functions to 6,372 genes, which allowed us to draw a bigger picture on how these genes contribute to male fertility. This study now opens the door for further in-depth studies to find key genes for R. prolixus reproductive biology.

genomics↗