Largest genetic study of mosquitoes reveals spread of insecticide resistance across Africa

Genetic resource will help develop new tools to support the campaign against malaria in Africa

Largest genetic study of mosquitoes reveals spread of insecticide resistance across Africa

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Populations of Anopheles gambiae mosquitoes sampled in Africa, by country. For full-sized image, please click here. Image: Nature DOI: 10.1038/nature24995

The largest-ever genetic study of mosquitoes reveals the movement of insecticide resistance between different regions of Africa and finds several rapidly evolving insecticide resistance genes. Reported today (29 November) in Nature, this genetic resource will be used to develop new tools for monitoring resistance and managing insecticide use, and for designing novel control methods.

Malaria is transmitted by mosquitoes and rising resistance to insecticides is hampering efforts to control the disease. The study by researchers from the Wellcome Trust Sanger Institute and their collaborators also discovered that wild mosquitoes collected in Africa were genetically far more diverse than had been thought. This helps to explain how mosquitoes evolve insecticide resistance so quickly.

More than 200 million people are infected with the malaria parasite worldwide each year, which is transmitted by blood-sucking Anopheles mosquitoes. Malaria caused the deaths of around 429,000 people in 2015* with the majority of cases in sub-Saharan Africa.

Public health measures in Africa such as insecticide-treated bed nets and insecticide-spraying have helped reduce the numbers of malaria cases since 2000, but many mosquitoes have evolved resistance to insecticides. This is now threatening to derail malaria control in Africa.

To understand how mosquitoes are evolving, researchers working with the Anopheles gambiae 1000 genomes project sequenced the DNA of 765 wild Anopheles mosquitoes. These were taken from 15 locations across eight African countries, creating the largest data resource on natural genetic variation for any species of insect. They then examined each of the mosquito genomes.

The researchers revealed that the Anopheles gambie mosquitoes are extremely genetically diverse compared with most other animal species. High genetic diversity enables rapid evolution and the study found 52 million small differences amongst the mosquito genomes.

“The diversity of mosquito genomes was far greater than we expected. Such high levels of genetic variation poise mosquito populations to rapidly evolve in response to our efforts to control them whether that be with insecticides or any other control measure, including gene drive.”

Dr Mara Lawniczak, a corresponding author on the paper and Faculty at the Wellcome Trust Sanger Institute

New strategies to control mosquitoes are being developed that use ‘gene drive’– using the latest Crispr/Cas 9 genetic tools to make mosquitoes infertile or unable to carry the malaria parasite. However, this technology requires an exact match with any targeted gene. The researchers found that gene drive is unlikely to work for most mosquito genes because they are too variable in nature, however they also used the data to highlight less variable targets that are potentially more suitable for gene drive based methods to control mosquitoes.

The mosquito genomes also revealed rapid evolution of several genes that had previously been implicated in insecticide resistance. Unexpectedly, the researchers discovered many previously-unknown genetic variants within those genes that could be causing insecticide resistance. Worryingly, they showed that these genetic variants for insecticide resistance were not only emerging independently in different parts of Africa, but were also being spread across the continent by mosquito migration.

“We know that mosquito populations are rapidly evolving resistance to insecticides, which is a serious threat to the future of malaria control in Africa. We have been able to see that a diverse array of genes linked to insecticide resistance are under very strong selection, confirming that they are playing an important role in the evolution of insecticide resistance in natural mosquito populations. Our study highlights the severe challenges facing public efforts to control mosquitoes and to manage and limit insecticide resistance.”

Professor Martin Donnelly, a corresponding author from the Liverpool School of Tropical Medicine and Honorary Faculty at the Wellcome Trust Sanger Institute

“The data we have generated are a unique resource for studying how mosquito populations are responding to our current control efforts, and for designing better technologies and strategies for mosquito control in the future. More data will be needed to fill in the geographical gaps and study how mosquito populations change over time and in response to specific control interventions. However, this study demonstrates a clear path towards building a new and much-needed source of intelligence to support the campaign to eradicate malaria in Africa.”

Alistair Miles, lead author from the University of Oxford and the Wellcome Trust Sanger Institute

Notes to Editors
Publication

The Anopheles gambiae 1000 Genomes Consortium. Genetic diversity of the African malaria vector Anopheles gambiae. (2017) Nature DOI: 10.1038/nature24995

*WHO stats on malaria http://www.who.int/features/factfiles/malaria/en/
For more information about malaria please see https://www.yourgenome.org/facts/what-is-malaria

Funding:

This work was supported by the Wellcome Trust, Medical Research Council UK, the Department for International Development, the Foundation for the National Institutes of Health through the Vector-Based Control of Transmission: Discovery Research (VCTR) program of the Grand Challenges in Global Health initiative of the Bill & Melinda Gates Foundation and the National Institute of Allergy and Infectious Diseases (NIAID).

Participating Centres:
  • Malaria Programme, Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
  • MRC Centre for Genomics and Global Health, University of Oxford, Oxford OX3 7BN, UK.
  • Instituto Pasteur Italia – Fondazione Cenci Bolognetti, Dipartimento di Sanita Pubblica e Malattie Infettive, Università di Roma SAPIENZA, Rome, Italy.
  • Department of Vector Biology,Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.
  • University of Montana, Missoula, Montana 59812, USA.
  • Department of Genetics, Rutgers University, 604 Alison Road, Piscataway, New Jersey 08854, USA.
  • Genome Sequencing and Analysis Program, Broad Institute, 415 Main Street, Cambridge, Maryland 02142, USA.
  • Department of Entomology, Virginia Tech, Blacksburg, Virginia 24061, USA.
  • Laboratory of Ecology, Genetics and Environmental Protection, Tomsk State University, Tomsk 634050, Russia.
  • Eck Institute for Global Health, Department of Biological Sciences, University of Notre Dame, Indiana 46556, USA.
  • Groningen Institute for Evolutionary Life Sciences (GELIFES), Nijenborgh 7, 9747 AG Groningen, The Netherlands.
  • Unité d’Ecologie des Systèmes Vectoriels, Centre International de Recherches Médicales de Franceville, Franceville, Gabon.
  • Institut de Recherche pour le Développement (IRD), UMR MIVEGEC (UM1, UM2, CNRS 5290, IRD 224), Montpellier, France.
  • Department of Life Sciences, Imperial College, Silwood Park, Ascot, Berkshire SL5 7PY, UK.
  • Department of Zoology, University of Oxford, The Tinbergen Building, South Parks Road, Oxford OX1 3PS, UK.
  • Department of Biology and School of Informatics and Computing, Indiana University, Bloomington, Indiana 47405, USA.
  • KEMRI-Wellcome Trust Research Programme, PO Box 230, Bofa Road, Kilifi, Kenya. 18Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, UNL, Rua da Junqueira 100, 1349-008 Lisbon, Portugal.
  • Department of Microbiology and Immunology, Microbial and Plant Genomics Institute, University of Minnesota, St Paul, Minnesota 55108, USA.
  • Unit for Genetics and Genomics of Insect Vectors, Institut Pasteur, Paris, France.
  • School of Natural Sciences and Psychology, Liverpool John Moores University, Liverpool L3 3AF, UK.
  • Department of Entomology, University of California, Riverside, California, USA.
  • Programa Nacional de Controle da Malária, Direcção Nacional de Saúde Pública, Ministério da Saúde, Luanda, Angola.
  • Institut de Recherche en Sciences de la Santé (IRSS), Bobo Dioulasso, Burkina Faso.
  • Laboratoire de Recherche sur le Paludisme, Organisation de Coordination pour la lutte contre les Endémies en Afrique Centrale (OCEAC),Yaoundé, Cameroon.
  • Malaria Research and Training Centre (MRTC), University of Bamako, Mali.
  • Instituto Nacional de Saúde Pública, Ministério da Saúde Pública, Bissau, Guiné-Bissau.
  • Infectious Diseases Research Collaboration, 2C Nakasero Hill Road, PO Box 7475, Kampala, Uganda.
  • The Broad Institute of Massachusetts Institute of Technology and Harvard, 415 Main Street, Cambridge, Massachusetts 02142, USA.
Selected Websites
What is malaria?FactsWhat is malaria?
Spread by mosquitos, malaria is one of the most common infectious diseases and a global public health challenge.

Malaria ChallengeInteractivesMalaria Challenge
In Malaria Challenge you can explore the different stages of malaria and how scientists are trying to find new ways of preventing and treating this deadly tropical disease.

How is malaria treated and prevented?FactsHow is malaria treated and prevented?
Malaria is an entirely preventable and treatable disease if tackled early enough. However, there are growing problems with drug resistance that are posing a threat to the global fight against malaria.

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