Using next-generation sequencing to understand the diversity and dynamics of Anopheles populations
A keystone of malaria control is to prevent transmission by the Anopheles vector. Hopes of eventually eliminating malaria rely greatly on this, but the failure of previous efforts to eradicate malaria has taught us that it is not easily accomplished, particularly because of the ability of Anopheles populations to develop resistance to insecticides as their usage increases.
New technologies for large-scale sequencing provide unprecedented opportunities to overcome insecticide resistance by real-time monitoring of genome variation in Anopheles populations, and using this information to develop early warning systems and other practical applications in vector control.
One such practical application is to understand the nature and scale of a mosquito breeding unit, and to describe rates and patterns of mosquito migration between different breeding units. Underlying this problem is the fact that human malaria is transmitted by approximately 50 different species of mosquitoes, some of which are capable of breeding with each other, and that each species has a complex population structure. Understanding genome diversity within and between Anopheles species is central to solving this problem.
Other practical applications include genome-wide association studies to determine the molecular causation of insecticide resistance and mosquito refractoriness to Plasmodium infection; and supporting efforts to develop novel transgenic methods of vector control, by conducting population genetic studies to understand the process of gene flow in Anopheles populations.
MalariaGEN first became involved in the study of malaria vectors in 2008, when it formed a community project to investigate genome variation in Anopheles gambiae. Through this community project, MalariaGEN provided a central resource for high-throughput sequencing and informatics to a number of partner studies including:
- Liverpool School of Tropical Medicine, UK (Martin Donnelly, David Weetman, Craig Wilding)
- Institute Pasteur, Paris, France (Ken Vernick)
- Imperial College, London, UK (Austin Burt, Sam O’Loughlin, Mara Lawniczak, George Christophides, Fotis Kafatos)
This early work was the foundation for the establishment of a multi-centre consortium, the Anopheles gambiae 1000 Genomes (Ag1000G). Many of the samples sequenced and genotyped through the initial community project have been contributed to Ag1000G.
- Clarkson CS, Weetman D, et al. Adaptive introgression between Anopheles sibling species eliminates a major genomic island but not reproductive isolation. Nat Commun, 2014; Jun 25; 5: 4248. PMID: 24963649