Improved<i>Aedes aegypti</i>mosquito reference genome assembly enables biological discovery and vector control

Matthews, Benjamin J.; Dudchenko, Olga; Kingan, Sarah B.; Koren, Sergey; Antoshechkin, Igor; Crawford, Jacob E.; Glassford, William J.; Herre, Margaret; Redmond, Seth; Rose, Noah H.; Weedall, Gareth D.; Wu, Yang; Batra, Sanjit Singh; Brito-Sierra, Carlos A; Campbell, Corey L.; Chan, Saki; Cox, Eric; Evans, Benjamin R.; Fansiri, Thanyalak; Filipović, Igor; Fontaine, Albin; Gloria‐Soria, Andrea; Hall, Richard J.; Joardar, Vinita; Jones, Andrew K.; Kay, Raissa G. G.; Kodali, Vamsi K.; Lee, Joyce; Lycett, Gareth; Mitchell, Sara N.; Muehling, Jill; Murphy, Michael R.; Omer, Arina D.; Partridge, Frederick A.; Peluso, Paul; Aiden, Aviva Presser; Ramasamy, Vidya; Rašić, Gordana; Roy, Sourav; Saavedra-Rodríguez, Karla; Sharan, Shruti; Sharma, Atashi; Smith, Melissa; Turner, Joe; Weakley, Allison M.; Zhao, Zhilei; Akbari, Omar S.; Black, William C.; Cao, Han; Darby, Alistair C.; Hill, Catherine A.; Johnston, Spencer; Raikhel, Alexander S.; Sattelle, David B.; Sharakhov, Igor V.; White, Bradley J.; Zhao, Li; Mann, Richard S.; Lambrechts, Louis; Powell, Jeffrey R.; Tu, Zhijian; Robertson, Hugh M.; McBride, Carolyn S.; Hastie, Alex; Korlach, Jonas; Neafsey, Daniel E.; Phillippy, Adam M.; Vosshall, Leslie B.

doi:10.1101/240747

Cited by 24 publications

(26 citation statements)

References 144 publications

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“…These observations reinforce previous conclusions from analyses of subsets of these genes 15,[26][27][28] that the non-antennal IRs function to detect a myriad of chemical stimuli to evoke a variety of behavioural responses. Such properties presumably apply to the vast, divergent IR repertoires of other insect species 15 , for example, the 455 family members of the German cockroach Blatella germanica 18 , or the 135 IRs of the mosquito Aedes aegypti 48 . Within Drosophila we did not detect obvious relationships between IR phylogeny and stage-or organ-specific expression patterns.…”

Section: Discussionmentioning

confidence: 99%

An expression atlas of chemosensory ionotropic glutamate receptors identifies a molecular basis of carbonation detection

Sánchez-Alcañiz

Silbering

Croset

et al. 2018

Preprint

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Taste perception is thought to involve the encoding of appetitive and aversive chemical cues in food through a limited number of sensory pathways. Through expression analysis of the complete repertoire of Drosophila Ionotropic Receptors (IRs), a sensory subfamily of ionotropic glutamate receptors, we reveal that the majority of IRs is expressed in diverse peripheral neuron populations across gustatory organs in both larvae and adults, implying numerous roles in taste-evoked behaviours. We characterise Ir56d, which labels two anatomically-distinct classes of neurons in the proboscis: one represents a subset of sugar-and fatty acid-sensing neurons, while the other responds to carbonated solutions and fatty acids. Mutational analysis shows that IR56d, together with the broadly-expressed co-receptors IR25a and IR76b, is essential for physiological activation by carbonation and fatty acids, but not sucrose. We further demonstrate that carbonation is behaviourally attractive to flies (in an IR56d-dependent manner), but in a distinct way to other appetitive stimuli. Our work provides a valuable toolkit for investigating the taste functions of IRs, defines a molecular basis of carbonation sensing, and illustrates how the gustatory system uses combinatorial expression of sensory receptors in distinct neuron types to coordinate behaviour.Classic models of gustatory perception in mammals highlight the existence of a small number of taste classes signalling nutritive content (e.g., sugars and amino acids) or toxicity (e.g., bitter) that determine -through activation of hard-wired neural circuits -behavioural acceptance or rejection of food 1, 2 . Different classes of tastants are recognised by discrete sensory channels that express distinct, and relatively small, receptor families. For example, detection of all sugars depends upon a single heterodimeric GPCR complex (T1R2/T1R3), while "bitter" cells -which detect an enormous diversity of noxious compounds -co-express a few dozen GPCRs of the T2R family 1, 2 . Such models have been pervasive in interpreting how gustatory perception occurs in other animals, including insects, where analogous segregated sensory pathways for sweet and bitter compounds have been defined [3][4][5][6] . However, in contrast to mammals, where taste -mediated by lingual taste buds -informs only feeding decisions, insect gustation occurs in multiple sensory appendages, including the proboscis, legs, wings and sexual organs, and controls diverse behaviours, such as foraging, feeding, sexual/social recognition and oviposition [3][4][5][6] . In addition to stereotyped appetitive and aversive feeding responses to sweet and bitter compounds respectively, insects display behavioural reactions to many other types of chemicals, including salt 7 , water 8 , carbonation (i.e., aqueous CO 2 ) 9 , organic and inorganic acids 10,11 , and pheromonal cuticular hydrocarbons 12 . The wide-ranging roles of the insect gustatory system are concordantly reflected in the underlying molecular receptors that mediate...

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Section: Discussionmentioning

confidence: 99%

An expression atlas of chemosensory ionotropic glutamate receptors identifies a molecular basis of carbonation detection

Sánchez-Alcañiz

Silbering

Croset

et al. 2018

Preprint

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“…Many satellite repeats are actively transcribed, and some of them produce small interfering (si)RNAs required for the establishment and maintenance of heterochromatic regions 9-16 . Around two-thirds of the genome of Aedes aegypti , the most important vector for arthropod-borne viruses like dengue, Zika, and yellow fever virus, consists of repetitive elements 17 (Extended Data Fig 1A), making this mosquito an interesting model to study these sequences. We analyzed small RNAs derived from unique and repetitive sequences in the genome of Ae.…”

Section: Mainmentioning

confidence: 99%

An ancient satellite repeat controls gene expression and embryonic development inAedes aegyptithrough a highly conserved piRNA

Halbach

Miesen

Joosten

et al. 2020

Preprint

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26Tandem repeat elements such as the highly diverse class of satellite repeats occupy large parts of 27 eukaryotic chromosomes. Most occur at (peri)centromeric and (sub)telomeric regions and have 28 been implicated in chromosome organization, stabilization, and segregation 1 . Others are located 29 more dispersed throughout the genome, but their functions remained largely enigmatic. Satellite 30 repeats in euchromatic regions were hypothesized to regulate gene expression in cis by modulation 31 of the local heterochromatin, or in trans via repeat-derived transcripts 2,3 . Yet, due to a lack of 32 experimental models, gene regulatory potential of satellite repeats remains largely unexplored. Here 33 we show that, in the vector mosquito Aedes aegypti, a satellite repeat promotes sequence-specific 34 gene silencing via the expression of two abundant PIWI-interacting RNAs (piRNAs). Strikingly, 35whereas satellite repeats and piRNA sequences generally evolve extremely fast 4-6 , this locus was 36 conserved for approximately 200 million years, suggesting a central function in mosquito biology. 37Tandem repeat-derived piRNA production commenced shortly after egg-laying and inactivation of 38 the most abundant of the two piRNAs in early embryos resulted in an arrest of embryonic 39 development. Transcriptional profiling in these embryos revealed the failure to degrade maternally 40 provided transcripts that are normally cleared during maternal-to-zygotic transition. Our results 41 reveal a novel mechanism in which satellite repeats regulate global gene expression in trans via 42 piRNA-mediated gene silencing, which is fundamental to embryonic development. These findings 43 highlight the regulatory potential of this enigmatic class of repeats. 44 45Main 46Even though satellite repeats have been discovered nearly 60 years ago 7,8 , and comprise a 47 substantial portion of eukaryotic genomes, little is known about the functions of this class of 48 repetitive DNA. Many satellite repeats are actively transcribed, and some of them produce small 49 interfering (si)RNAs required for the establishment and maintenance of heterochromatic regions 9-16 . 50

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“…Sequencing data then was blasted to the AaegL5.0 reference genome 70 were mapped to the Ae. aegypti genome (AaegL5.0) supplemented with the 1C19 cDNA sequence using STAR aligner 71 , and the expression levels were determined with featureCounts 72 ( Supplementary Table S4).…”

Section: Characterization Of Insertion Sitesmentioning

confidence: 99%

Broad Dengue Neutralization in Mosquitoes Expressing an Engineered Antibody

Buchman

Gamez

et al. 2019

Preprint

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With dengue virus (DENV) becoming endemic in tropical and subtropical regions worldwide, there is a pressing global demand for effective strategies to control the mosquitoes that spread this disease. Recent advances in genetic engineering technologies have made it possible to create mosquitoes with reduced vector competence, limiting their ability to acquire and transmit pathogens. Here we describe the development of Aedes aegypti mosquitoes synthetically engineered to impede vector competence to DENV. These mosquitoes express a gene encoding an engineered single-chain variable fragment derived from a broadly neutralizing DENV human monoclonal antibody and have significantly reduced viral infection, dissemination, and transmission rates for all four major antigenically distinct DENV serotypes. Importantly, this is the first engineered approach that targets all DENV serotypes, which is crucial for effective disease suppression. These results provide a compelling route for developing effective genetic-based DENV control strategies, which could be extended to curtail other arboviruses. Significance StatementHere we describe the development of Ae. aegypti mosquitoes synthetically engineered to impede vector competence to multiple serotypes of DENV. Given the global significance of DENV, these mosquitoes may be used to curtail Dengue transmission by this potent vector.

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ImprovedAedes aegyptimosquito reference genome assembly enables biological discovery and vector control

Cited by 24 publications

References 144 publications

An expression atlas of chemosensory ionotropic glutamate receptors identifies a molecular basis of carbonation detection

An expression atlas of chemosensory ionotropic glutamate receptors identifies a molecular basis of carbonation detection

An ancient satellite repeat controls gene expression and embryonic development inAedes aegyptithrough a highly conserved piRNA

Broad Dengue Neutralization in Mosquitoes Expressing an Engineered Antibody

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