The fight against infectious disease is a race against evolution. Bacteria become resistant to antibiotics. Viruses adapt to spread more quickly. Diseases transmitted by insects present another evolutionary front: Insects themselves can evolve resistance to the poisons that people use to kill them.In particular, the mosquito-borne disease malaria kills over 600,000 people annually. Since World War II, people have battled malaria with insecticides – chemical weapons intended to kill Anopheles mosquitoes infected with the Plasmodium parasites that cause the disease.However, mosquitoes are quickly evolving counterstrategies that make these insecticides ineffective, putting millions of people at greater risk of deadly infection. My colleagues and I have newly published research showing how.Insecticide resistance threatens public healthAs an evolutionary geneticist, I study natural selection – the basis for adaptive evolution. Genetic variants that best promote survival can replace less advantageous versions, causing species to change. Anopheles mosquitoes are frustratingly adept at evolving.AdvertisementAdvertisementIn the mid-1990s, most African Anopheles were susceptible to pyrethroids, a popular type of insecticide originally derived from chrysanthemums. Anopheles control relies on two pyrethroid-based methods: insecticide-treated bed nets to protect sleepers, and indoor residual spraying of insecticide against the walls of homes. These two methods alone likely prevented over a half-billion cases of malaria between 2000 and 2015.However, mosquitoes today from Ghana to Malawi are often able to survive insecticide concentrations 10 times the previously lethal dose. Along with Anopheles control efforts, agriculture also inadvertently exposes mosquitoes to pyrethroids and contributes to insecticide resistance.In some African locales, Anopheles is already showing resistance to all four main classes of insecticide used for malaria control.Adaptation in Latin American mosquitoesAnopheles mosquitoes and the malaria-causing Plasmodium also occur outside Africa, where insecticide resistance is less well-researched.AdvertisementAdvertisementIn much of South America, the main malaria vector is Anopheles darlingi. This mosquito species has diverged evolutionarily from the African vectors so extensively that it might be a different genus, Nyssorhynchus. Along with colleagues from eight countries, I analyzed over 1,000 Anopheles darlingi genomes to understand its genetic diversity, including any recent changes due to human activity. My collaborators collected these mosquitoes at 16 locations ranging from the Atlantic coast of Brazil to the Pacific side of the Andes in Colombia.We found that, like its African counterparts, Anopheles darlingi shows extremely high genetic diversity – more than 20 times that of humans – indicating that very large populations of this insect exist. A species with such a vast gene pool is well poised to adapt to new challenges. The right mutation giving it the advantage it needs is more likely to pop up when there are so many individuals. And once that mutation starts to spread, it’s protected by numbers since it won’t be wiped out if a few mosquitoes die by chance.In contrast, bald eagles in the contiguous U.S. were never able to evolve resistance against the insecticide DDT and approached extinction. Evolution is more efficient among millions of insects than mere thousands of birds. And indeed, we saw signals of adaptive evolution in the resistance-related genes of Anopheles darlingi occurring over the past few decades.Mosquitoes evolve to detoxify poisonsInsecticides like pyrethroids and DDT share the same molecular target: channels in nerve cells that can open and close. When open, the nerve cell stimulates other cells. These insecticides force the channels to remain open and continuously fire, causing paralysis and death. However, insects can evolve resistance by changing the shape of the channel itself.AdvertisementAdvertisementEarlier genetic scans performed by other researchers had not detected this type of resistance in Anopheles darlingi, and neither did ours. Instead, we found that resistance is evolving in another way: a group of genes encoding enzymes that break down toxic compounds. High activity of these enzymes, called P450, frequently underlies resistance to insecticides in other mosquitoes. The same cluster of P450 genes has changed independently at least seven times across South America since insecticide use began in the mid-20th century.More in ScienceIn French Guiana, a different set of P450 genes exhib …
