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Genome analysis of a major urban malaria vector mosquito, Anopheles stephensi.

ABSTRACT: Anopheles stephensi is the key vector of malaria throughout the Indian subcontinent and Middle East and an emerging model for molecular and genetic studies of mosquito-parasite interactions. The type form of the species is responsible for the majority of urban malaria transmission across its range.Here, we report the genome sequence and annotation of the Indian strain of the type form of An. stephensi. The 221 Mb genome assembly represents more than 92% of the entire genome and was produced using a combination of 454, Illumina, and PacBio sequencing. Physical mapping assigned 62% of the genome onto chromosomes, enabling chromosome-based analysis. Comparisons between An. stephensi and An. gambiae reveal that the rate of gene order reshuffling on the X chromosome was three times higher than that on the autosomes. An. stephensi has more heterochromatin in pericentric regions but less repetitive DNA in chromosome arms than An. gambiae. We also identify a number of Y-chromosome contigs and BACs. Interspersed repeats constitute 7.1% of the assembled genome while LTR retrotransposons alone comprise more than 49% of the Y contigs. RNA-seq analyses provide new insights into mosquito innate immunity, development, and sexual dimorphism.The genome analysis described in this manuscript provides a resource and platform for fundamental and translational research into a major urban malaria vector. Chromosome-based investigations provide unique perspectives on Anopheles chromosome evolution. RNA-seq analysis and studies of immunity genes offer new insights into mosquito biology and mosquito-parasite interactions.

SUBMITTER: Jiang X

PROVIDER: S-EPMC4195908 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Genome analysis of a major urban malaria vector mosquito, Anopheles stephensi.

Jiang Xiaofang X Peery Ashley A Hall A Brantley AB Sharma Atashi A Chen Xiao-Guang XG Waterhouse Robert M RM Komissarov Aleksey A Riehle Michelle M MM Shouche Yogesh Y Sharakhova Maria V MV Lawson Dan D Pakpour Nazzy N Arensburger Peter P Davidson Victoria L M VL Eiglmeier Karin K Emrich Scott S George Phillip P Kennedy Ryan C RC Mane Shrinivasrao P SP Maslen Gareth G Oringanje Chioma C Qi Yumin Y Settlage Robert R Tojo Marta M Tubio Jose M C JM Unger Maria F MF Wang Bo B Vernick Kenneth D KD Ribeiro Jose M C JM James Anthony A AA Michel Kristin K Riehle Michael A MA Luckhart Shirley S Sharakhov Igor V IV Tu Zhijian Z

Genome biology 20140923 9

<h4>Background</h4>Anopheles stephensi is the key vector of malaria throughout the Indian subcontinent and Middle East and an emerging model for molecular and genetic studies of mosquito-parasite interactions. The type form of the species is responsible for the majority of urban malaria transmission across its range.<h4>Results</h4>Here, we report the genome sequence and annotation of the Indian strain of the type form of An. stephensi. The 221 Mb genome assembly represents more than 92% of the ...[more]

PMID: 25244985

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Project description:Small laboratory cage trials of non-drive and gene-drive strains of the Asian malaria vector mosquito, Anopheles stephensi, were used to investigate release ratios and other strain properties for their impact on transgene spread during simulated population modification. We evaluated the effects of transgenes on survival, male contributions to next-generation populations, female reproductive success and the impact of accumulation of gene drive-resistant genomic target sites resulting from nonhomologous end-joining (NHEJ) mutagenesis during Cas9, guide RNA-mediated cleavage. Experiments with a non-drive, autosomally-linked malaria-resistance gene cassette showed 'full introduction' (100% of the insects have at least one copy of the transgene) within 8 weeks (? 3 generations) following weekly releases of 10:1 transgenic:wild-type males in an overlapping generation trial design. Male release ratios of 1:1 resulted in cages where mosquitoes with at least one copy of the transgene fluctuated around 50%. In comparison, two of three cages in which the malaria-resistance genes were linked to a gene-drive system in an overlapping generation, single 1:1 release reached full introduction in 6-8 generations with a third cage at ~80% within the same time. Release ratios of 0.1:1 failed to establish the transgenes. A non-overlapping generation, single-release trial of the same gene-drive strain resulted in two of three cages reaching 100% introduction within 6-12 generations following a 1:1 transgenic:wild-type male release. Two of three cages with 0.33:1 transgenic:wild-type male single releases achieved full introduction in 13-16 generations. All populations exhibiting full introduction went extinct within three generations due to a significant load on females having disruptions of both copies of the target gene, kynurenine hydroxylase. While repeated releases of high-ratio (10:1) non-drive constructs could achieve full introduction, results from the 1:1 release ratios across all experimental designs favor the use of gene drive, both for efficiency and anticipated cost of the control programs.

Dataset Information

Genome analysis of a major urban malaria vector mosquito, Anopheles stephensi.

Publications

Genome analysis of a major urban malaria vector mosquito, Anopheles stephensi.

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