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Sharakhova, M. V.

Publications and source records attributed to Sharakhova, M. V..

9 recordsLinked to original sources

Discovery and characterization of chromosomal inversions in the arboviral vector mosquito Aedes aegypti

Chromosomal inversions play a fundamental role in evolution and have been shown to regulate epidemiologically important traits in malaria mosquitoes. However, they have never been characterized in Aedes aegypti, the major vector of arboviruses, because of the poor structure of its polytene chromosomes. In this study, we applied a Hi-C proximity ligation approach to identify chromosomal inversions in 25 strains of Ae. aegypti, acquired from its worldwide distribution, as well as in one strain of Ae. mascarensis. The study identified 21 multi-megabase inversions with uneven distributions along the three chromosomes. All chromosomal inversions, including one specific for Ae. mascarensis, were polymorphic. Nevertheless, geographic origin separated the strains into two clusters carrying African and non-African inversions suggesting their potential association with Ae. aegypti subspecies. Some of the inversions colocalized with chemoreceptor genes and quantitative trait loci associated with pathogen infection, implicating the potential role of inversions in host choice and disease transmission.

evolutionary biology↗

Molecular signature of domestication in the arboviral vector Aedes aegypti

BackgroundDomestication is a complex, multi-stage and species-specific process that results in organisms living close to humans. In the arboviral vector Aedes aegypti adaptation to living in proximity with anthropogenic environments has been recognized as a major evolutionary shift, separating a generalist form, Aedes aegypti formosus (Aaf), from the domestic form Aedes aegypti aegypti (Aaa), which tends to deposit eggs artificial containers and bite humans for a blood meal. These behaviors enhance the mosquito vectorial capacity. The extent to which domestication has impacted the Ae. aegypti genome has not been thoroughly investigated yet. ResultsTaking advantage of two forms distinct and historically documented geographic distributions, we analyzed the genomes of 634 worldwide Ae. aegypti mosquitoes. Using more than 300 million high-confidence SNPs, we found a unique origin for all out-of-Africa Ae. aegypti mosquitoes, with no evidence of admixture events in Africa, apart from Kenya. A group of genes were under positive selection only in out-of-Africa mosquitoes and 236 genes had nonsynonymous mutations, occurring at statistically different frequencies in Aaa and Aaf mosquitoes. ConclusionWe identified a clear signal of genetic differentiation between Aaa and Aaf, circumscribed to a catalogue of candidate genes. These "Aaa molecular signature" genes extend beyond chemosensory genes to genes linked to neuronal and hormonal functions. This suggests that the behavioral shift to domestication may rely on the fine regulation of metabolic and neuronal functions, more than the role of a few significant genes. Our results also provide the foundation to investigate new targets for the control of Ae. aegypti populations.

evolutionary biology↗

Patterns of genetic differentiation imply distinct evolutionary histories of the sibling mosquito species Anopheles messeae and Anopheles daciae in Eurasia

Detailed knowledge of phylogeography is important for control of mosquito species involved in transmission of human infectious diseases. Anopheles messeae is a geographically widespread and genetically diverse dominant vector of malaria in Eurasia. A closely related sibling species, An. daciae, was distinguished from An. messeae based on a few nucleotide differences in its ribosomal DNA. However, the mechanisms of speciation and their evolutionary histories are poorly understood. Here, we performed a large-scale population genetics analysis of 3694 mosquitos from Eurasia to understand the species divergence, diversity, and population structure using the Internal Transcribed Spacer 2 of ribosomal DNA for species identification and frequencies of 11 polymorphic chromosomal inversions as genetic markers. The study revealed striking differences in the geographical distribution of the sibling species. The largest genetic differences between An. messeae and An. daciae were detected in the X sex chromosome suggesting that this chromosome plays a role in speciation. The frequencies of autosomal inversions differed significantly between the species, strongly supporting a restricted gene flow. The clinal variability of some inversion frequencies was revealed in both species implicating their possible involvement in climate adaptations. Statistical analysis of inversion polymorphism clearly distinguished two clusters associated with the two species and demonstrated much higher genetic diversity within An. messeae. Overall, the frequencies of hybrids in all locations were extremely low with the exception of several southeastern populations, where putative hybrids were abundant. Thus, the pattern of genetic differentiation implies dramatic differences in geographic distribution, population structure, and evolutionary histories of the sibling species An. messeae and An. daciae.

evolutionary biology↗

Phylogenomics revealed migration routes and adaptive radiation timing of Holarctic malaria vectors of the Maculipennis group

BackgroundUnderstanding the evolutionary relationships between closely related taxa is important for mosquitoes that transmit human diseases. Six out of 41 dominant malaria vectors in the world belong to the Maculipennis group, which is subdivided into two North American subgroups (Freeborni and Quadrimaculatus), and one Eurasian (Maculipennis) subgroup. Although previous studies considered the Nearctic subgroups as ancestral, details about their relationship with the Palearctic subgroup, and their migration times and routes from North America to Eurasia remain controversial. The Eurasian species An. beklemishevi is currently included in the North American Quadrimaculatus subgroup adding to the uncertainties in mosquito systematics. ResultsTo reconstruct historic relationships between the North American and Eurasian mosquitoes, we conducted a phylogenomic analysis of 11 Palearctic and 2 Nearctic species based on 1271 orthologous genes using their transcriptomic or genomic sequences. The analysis indicated that the Palearctic species An. beklemishevi clusters together with other Eurasian species and represents a basal lineage among them. Also, An. beklemishevi is related more closely to An. freeborni, which inhabits the Western United States, rather than to An. quadrimaculatus, a species from the Eastern United States. The time-calibrated tree suggests a migration of mosquitoes in the Maculipennis group from North America to Eurasia about 20-25 million years ago through the Bering Land Bridge. A Hybridcheck analysis demonstrated highly significant signatures of introgression events between allopatric species An. labranchiae and An. beklemishevi. The analysis also identified ancestral introgression events between An. sacharovi and its Nearctic relative An. freeborni despite their current geographic isolation. ConclusionsOur phylogenomic analyses reveal migration routes and adaptive radiation timing of Holarctic malaria vectors and strongly support inclusion of An. beklemishevi into the Maculipennis subgroup. The vectorial capacity and the ability to diapause during winter evolved multiple times in Maculipennis evolution. Detailed knowledge of the evolutionary history in the Maculipennis subgroup will help us better understand the current and future patterns of malaria transmission in Eurasia.

evolutionary biology↗

Improved reference genome of the arboviral vector Aedes albopictus

The Asian tiger mosquito Aedes albopictus is globally expanding and has become the main vector for human arboviruses in Europe. Here we present AalbF2, a dramatically improved assembly of the Ae. albopictus genome that has revealed widespread viral insertions, novel microRNAs and piRNA clusters, the sex determining locus, new immunity genes, and has enabled genome-wide studies of geographically diverse Ae. albopictus populations and analyses of the developmental and stage-dependent network of expression data. Additionally, we built the first physical map for this species with 75% of the assembled genome anchored to the chromosomes. These up-to-date resources of the genome provide a foundation to improve understanding of the adaptation potential and the epidemiological relevance of this species and foster the development of innovative control measures. One Sentence SummaryLong-read and Hi-C-based de novo assembly of the arboviral vector Aedes albopictus genome fosters deeper understanding of its biological features.

genomics↗

Genomic differentiation and intercontinental population structure of mosquito vectors Culex pipiens pipiens and Culex pipiens molestus

Understanding the population structure and mechanisms of taxa diversification is important for organisms responsible for the transmission of human diseases. Two vectors of West Nile virus, Culex pipiens pipiens and Cx. p. molestus, exhibit epidemiologically important behavioral and physiological differences, but the whole-genome divergence between them was unexplored. In this study, we re-sequenced and compared the whole genomes of 40 individual mosquitoes from four locations in Eurasia and North America: the Republic of Belarus, the Kyrgyz Republic, and the United States of America. Principal Component, ADMIXTURE, and neighbor joining analyses of the nuclear genomes identified two intercontinental, monophyletic clusters of Cx. p. pipiens and Cx. p. molestus. The third cluster, having a polyphyletic origin, was formed by Cx. p. pipiens and Cx. quinquefasciatus from the USA. The level of genomic differentiation between the subspecies was uniform along chromosomes. The ADMIXTURE analysis determined signatures of admixture in all Cx. p. pipens populations but not in Cx. p. molestus populations. Comparison of mitochondrial genomes among the specimens showed a paraphyletic origin of the major haplogroups between the subspecies but a monophyletic structure between the continents. Thus, our study identified that Cx. p. molestus and Cx. p. pipiens represent different evolutionary units with monophyletic origin that have undergone incipient ecological speciation.

genomics↗

Nix confers heritable sex-conversion in Aedes aegypti and myo-sex is needed for male flight

A dominant and hemizygous male-determining locus (M locus) establishes the male sex (M/m) in the yellow fever mosquito, Aedes aegypti. Nix is a male-determining factor (M factor) in the M locus and its transient expression in females (m/m) results in partial masculinization. Here, we show that the Nix transgene alone was sufficient to convert females into fertile males, which continued to produce sex-converted progeny in subsequent generations. However, assisted mating with wild-type females was necessary, as the converted m/m males could not fly. Knockout of myo-sex, a myosin heavy chain gene and the only other protein-coding gene reported in the M locus, rendered wild-type males flightless. Thus, Nix alone converts female Ae. aegypti to fertile males and myo-sex is required for male flight. Only female Ae. aegypti mosquitoes bite and transmit disease-causing viruses. Nix-mediated female-to-male conversion is 100% penetrant and stable over many generations, indicating great potential for mosquito control.

developmental biology↗

Leveraging evolutionary relationships to improve Anopheles genome assemblies

While new sequencing technologies have lowered financial barriers to whole genome sequencing, resulting assemblies are often fragmented and far from finished. Subsequent improvements towards chromosomal-level status can be achieved by both experimental and computational approaches. Requiring only annotated assemblies and gene orthology data, comparative genomics approaches that aim to capture evolutionary signals to predict scaffold neighbours (adjacencies) offer potentially substantive improvements without the costs associated with experimental scaffolding or re-sequencing. We leverage the combined detection power of three such gene synteny-based methods applied to 21 Anopheles mosquito assemblies with variable contiguity levels to produce consensus sets of scaffold adjacency predictions. Three complementary validations were performed on subsets of assemblies with additional supporting data: six with physical mapping data; 13 with paired-end RNA sequencing (RNAseq) data; and three with new assemblies based on re-scaffolding or incorporating Pacific Biosciences (PacBio) sequencing data. Improved assemblies were built by integrating the consensus adjacency predictions with supporting experimental data, resulting in 20 new reference assemblies with improved contiguities. Combined with physical mapping data for six anophelines, chromosomal positioning of scaffolds improved assembly anchoring by 47% for A. funestus and 38% A. stephensi. Reconciling an A. funestus PacBio assembly with synteny-based and RNAseq-based adjacencies and physical mapping data resulted in a new 81.5% chromosomally mapped reference assembly and cytogenetic photomap. While complementary experimental data are clearly key to achieving high-quality chromosomal-level assemblies, our assessments and validations of gene synteny-based computational methods highlight the utility of applying comparative genomics approaches to improve community genomic resources.

genomics↗

Analysis of the Aedes albopictus C6/36 genome provides insight into cell line adaptations to in vitro viral propagation

BackgroundThe 50-year old Aedes albopictus C6/36 cell line is a resource for the detection, amplification, and analysis of mosquito-borne viruses including Zika, dengue, and chikungunya. The cell line is derived from an unknown number of larvae from an unspecified strain of Aedes albopictus mosquitoes. Toward improved utility of the cell line for research in virus transmission, we present an annotated assembly of the C6/36 genome.\n\nResultsThe C6/36 genome assembly has the largest contig N50 (3.3 Mbp) of any mosquito assembly, presents the sequences of both haplotypes for most of the diploid genome, reveals independent null mutations in both alleles of the Dicer locus, and indicates a male-specific genome. Gene annotation was computed with publicly available mosquito transcript sequences. Gene expression data from cell line RNA sequence identified enrichment of growth-related pathways and conspicuous deficiency in aquaporins and inward rectifier K+ channels. As a test of utility, RNA sequence data from Zika-infected cells was mapped to the C6/36 genome and transcriptome assemblies. Host subtraction reduced the data set by 89%, enabling faster characterization of non-host reads.\n\nConclusionsThe C6/36 genome sequence and annotation should enable additional uses of the cell line to study arbovirus vector interactions and interventions aimed at restricting the spread of human disease.

genomics↗