The regulatory genome of the malaria vector<i>Anopheles gambiae</i>: integrating chromatin accessibility and gene expression

Ruiz, José Luis; Ranford-Cartwright, Lisa; Gómez-Díaz, Elena

doi:10.1101/2020.06.22.164228

Cited by 8 publications

(18 citation statements)

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“…The chromatin accessibility and gene expression profiles obtained for this region in An. gambiae ( Ruiz et al, 2020 ) are included. According to Ruiz et al (2020) , lrim1 is differentially expressed between midguts and salivary glands, and this is associated with differential chromatin accessibility at the enhancer region (pink box).…”

Section: D Genome Organizationmentioning

confidence: 99%

“…gambiae ( Ruiz et al, 2020 ) are included. According to Ruiz et al (2020) , lrim1 is differentially expressed between midguts and salivary glands, and this is associated with differential chromatin accessibility at the enhancer region (pink box). Adapted from Ruiz et al (2020) .)…”

Section: D Genome Organizationmentioning

confidence: 99%

“…The histone modifications landscape seems to be generally well-conserved between Drosophila and Anopheles spp. ( Gómez-Díaz et al, 2014 ; Ruiz et al, 2019 ; Ruiz et al, 2020 ). Unfortunately, no available data exists for mosquito species of the genera Aedes and Culex .…”

Section: Chromatin Structure and Regulation Of Gene Expressionmentioning

confidence: 99%

“…gambiae ( Goltsev et al, 2007 ; Cande et al, 2009 ; Kazemian et al, 2014 ), or the cytochrome P450 Cyp9m10 gene involved in insecticide resistance in Cx. quinquefasciatus ( Itokawa et al, 2011 ; Wilding et al, 2012 ), the vast majority of mosquito CREs reported to date are computational predictions and/or still lack experimental verification ( Sieglaff et al, 2009 ; O’Brochta et al, 2012 ; Ahanger et al, 2013 ; Kazemian et al, 2014 ; Price et al, 2015 ; Behura et al, 2016 ; Perez-Zamorano et al, 2017 ; Mysore et al, 2018 ; Nardini et al, 2019 ; Ruiz et al, 2019 , 2020 ; Brody et al, 2020 ). The application of state-of-the-art methods for the genome-wide profiling of chromatin accessibility that allow the identification of functional CREs is therefore crucial.…”

Section: Chromatin Structure and Regulation Of Gene Expressionmentioning

confidence: 99%

“…A recent study using ATAC-seq in combination with RNA-seq in different An. gambiae tissues ( Ruiz et al, 2020 ) revealed a precise genome-wide map of CREs involved in the control of tissue-specific gene expression and predicted in vivo binding sites of relevant transcription factors. Results showed that a great portion of regulatory sites are located at introns, followed by those annotated to TSSs and exons, suggesting a predominant role of intragenic CREs in mosquito transcriptional regulation.…”

Section: Chromatin Structure and Regulation Of Gene Expressionmentioning

confidence: 99%

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Chromatin Structure and Function in Mosquitoes

et al. 2020

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The principles and function of chromatin and nuclear architecture have been extensively studied in model organisms, such as Drosophila melanogaster. However, little is known about the role of these epigenetic processes in transcriptional regulation in other insects including mosquitoes, which are major disease vectors and a worldwide threat for human health. Some of these life-threatening diseases are malaria, which is caused by protozoan parasites of the genus Plasmodium and transmitted by Anopheles mosquitoes; dengue fever, which is caused by an arbovirus mainly transmitted by Aedes aegypti; and West Nile fever, which is caused by an arbovirus transmitted by Culex spp. In this contribution, we review what is known about chromatin-associated mechanisms and the 3D genome structure in various mosquito vectors, including Anopheles, Aedes, and Culex spp. We also discuss the similarities between epigenetic mechanisms in mosquitoes and the model organism Drosophila melanogaster, and advocate that the field could benefit from the cross-application of state-of-the-art functional genomic technologies that are well-developed in the fruit fly. Uncovering the mosquito regulatory genome can lead to the discovery of unique regulatory networks associated with the parasitic life-style of these insects. It is also critical to understand the molecular interactions between the vectors and the pathogens that they transmit, which could hold the key to major breakthroughs on the fight against mosquito-borne diseases. Finally, it is clear that epigenetic mechanisms controlling mosquito environmental plasticity and evolvability are also of utmost importance, particularly in the current context of globalization and climate change.

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Section: D Genome Organizationmentioning

confidence: 99%

Section: D Genome Organizationmentioning

confidence: 99%

Section: Chromatin Structure and Regulation Of Gene Expressionmentioning

confidence: 99%

Section: Chromatin Structure and Regulation Of Gene Expressionmentioning

confidence: 99%

Section: Chromatin Structure and Regulation Of Gene Expressionmentioning

confidence: 99%

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Chromatin Structure and Function in Mosquitoes

et al. 2020

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Uncovering transposable element variants and their potential adaptive impact in urban populations of the malaria vectorAnopheles coluzzii

Vargas-Chávez

Pendy

Nsango

et al. 2020

Preprint

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BackgroundAnopheles coluzzii is one of the primary vectors of human malaria in sub-Saharan Africa. Recently, it has colonized the main cities of Central Africa threatening vector control programs. The adaptation of An. coluzzii to urban environments is partly due to an increased tolerance to organic pollution and insecticides. While some of the molecular mechanisms for ecological adaptation, including chromosome rearrangements and introgressions, are known, the role of transposable elements (TEs) in the adaptive processes of this species has not been studied yet.ResultsTo better understand the role of TEs in rapid urban adaptation, we sequenced using long-reads six An. coluzzii genomes from natural breeding sites in two major Central Africa cities. We de novo annotated the complete set of TEs and identified 64 previously undescribed families. TEs were non-randomly distributed throughout the genome with significant differences in the number of insertions of several superfamilies across the studied genomes. We identified seven putatively active families with insertions near genes with functions related to vectorial capacity. Moreover, we identified several TE insertions providing promoter and transcription factor binding sites to insecticide resistance and immune-related genes.ConclusionsThe analysis of multiple genomes sequenced using long-read technologies allowed us to generate the most comprehensive TE annotations in this species to date. We found that TEs have an impact in both the genome architecture and the regulation of functionally relevant genes in An. coluzzii. These results provide a basis for future studies of the impact of TEs on the biology of An. coluzzii.

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Identification of a rapidly-spreading triple mutant for high-level metabolic insecticide resistance inAnopheles gambiaeprovides a real-time molecular diagnostic for anti-malarial intervention deployment

Njoroge

Oruni

et al. 2021

Preprint

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Insecticide resistance provides both an increasingly pressing threat to the control of vector-borne diseases and insights into the remarkable capacity of natural populations to show rapid evolutionary responses to contemporary selection. Malaria control remains heavily dependent on deployment of pyrethroid insecticides, primarily in long lasting insecticide treated nets (LLINs), but resistance in the major malaria vectors has increased over the last 15 years in concert with dramatic expansion of LLIN distributions. Identifying genetic mechanisms causing high-level resistance in mosquitoes, which may almost entirely overcome pyrethroid efficacy, is crucial for the development and deployment of potentially resistance-breaking tools. Using the Anopheles gambiae 1000 genomes (Ag1000G) data we identified a very recent selective sweep in Ugandan mosquitoes which localized to a cluster of cytochrome P450 genes, including some frequently implicated in resistance. Further interrogation revealed a haplotype involving a trio of mutations, a nonsynonymous point mutation in Cyp6p4 (I236M), an upstream insertion of a partial Zanzibar transposable element (TE) and a duplication of the Cyp6aa1 gene. The mutations appear to have originated recently in An. gambiae from the Kenya-Uganda border region around lake Victoria, with stepwise replacement of the double-mutant (Zanzibar TE and Cyp6p4-236M) with the triple-mutant haplotype (including Cyp6aa1 duplication), which has spread into the Democratic Republic of Congo and Tanzania. The triple-mutant haplotype is strongly associated with increased expression of genes able to metabolise pyrethroids; is strongly predictive of resistance to pyrethroids most notably deltamethrin, a commonly-used LLIN insecticide, but importantly, appears less effective against LLINs co-treated with the synergist piperonyl butoxide (PBO). Frequencies of the triple-mutant haplotype remain spatially variable even within countries, suggesting an effective marker system to guide deployment decisions for limited supplies of PBO-pyrethroid co-treated LLINs across African countries. Duplications of Cyp6aa1 gene are common in An. gambiae across Africa and are likely to be a useful diagnostic for high levels of pyrethroid resistance.

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The regulatory genome of the malaria vectorAnopheles gambiae: integrating chromatin accessibility and gene expression

Abstract: 25Background: Anopheles gambiae mosquitoes are the primary vectors for the transmission 26

Cited by 8 publications

References 107 publications

Chromatin Structure and Function in Mosquitoes

Chromatin Structure and Function in Mosquitoes

Uncovering transposable element variants and their potential adaptive impact in urban populations of the malaria vectorAnopheles coluzzii

Identification of a rapidly-spreading triple mutant for high-level metabolic insecticide resistance inAnopheles gambiaeprovides a real-time molecular diagnostic for anti-malarial intervention deployment

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