The fight against infectious diseases is a race against evolution. Bacteria develop resistance to antibiotics, and viruses constantly evolve to spread faster. Insect-borne diseases represent another evolutionary battleground: insects themselves are developing resistance to the poisons humans use to kill them.
In particular, mosquito-borne malaria kills over 600,000 people annually. Since World War II, insecticides—chemical weapons designed to kill Anopheles mosquitoes infected with the malaria parasite—have been used to combat malaria.
However, mosquitoes quickly develop strategies to render these insecticides ineffective, exposing millions of people to increased risk of fatal infections. My recently published study, conducted with colleagues, explains why.
As an evolutionary geneticist, I study natural selection—the basis of adaptive evolution. Genetic variations that are most beneficial for survival replace those that are disadvantageous, leading to changes in species. The evolutionary capabilities of the Anopheles mosquito are truly astonishing.
In the mid-1990s, most Anopheles mosquitoes in Africa were susceptible to pyrethroid insecticides, originally derived from chrysanthemums. Mosquito control relied primarily on two pyrethroid-based methods: insecticide-treated mosquito nets to protect sleeping mosquitoes and residual insecticide sprays on building walls. These two methods alone likely prevented over 500 million cases of malaria between 2000 and 2015.
However, mosquitoes from Ghana to Malawi are now frequently developing resistance to pesticides at concentrations 10 times higher than the previously lethal dose. In addition to measures to control Anopheles mosquitoes, agricultural activities can inadvertently expose mosquitoes to pyrethroid insecticides, further exacerbating their resistance.
In some parts of Africa, Anopheles mosquitoes have developed resistance to four classes of insecticides used to control malaria.
Anopheles mosquitoes and malaria parasites are also found outside of Africa, where pesticide resistance research is less common.
In much of South America, the primary malaria vector is the Anopheles darlingi mosquito. This mosquito is so distinct from malaria vectors in Africa that it may belong to a different genus—Nyssorhynchus. Together with colleagues from eight countries, I analyzed the genomes of over 1,000 Anopheles darlingi mosquitoes to understand their genetic diversity, including any changes caused by recent human activity. My colleagues collected these mosquitoes from 16 locations across a vast territory stretching from the Atlantic coast of Brazil to the Pacific coast of the Andes in Colombia.
We found that, like its African relatives, *Anopheles darlingi* exhibits extremely high genetic diversity—more than 20 times that of humans—indicating a very large population. Species with such a large gene pool are well-adapted to adapt to new challenges. When a population is so large, the likelihood of the emergence of appropriate mutations that provide a desired advantage increases. Once this mutation begins to spread, thanks to the numerical advantage, even the random death of a few mosquitoes will not lead to its complete extinction.
In contrast, the bald eagle, native to the United States, never developed resistance to the insecticide DDT and ultimately faced extinction. The evolutionary efficiency of millions of insects far exceeds that of just a few thousand birds. In fact, over the past few decades, we have observed signs of adaptive evolution in genes associated with drug resistance in Anopheles darlingi mosquitoes.
Pyrethroids and DDT, among other insecticides, act on the same molecular target: ion channels that can open and close in nerve cells. When these channels are open, nerve cells stimulate other cells. Insecticides force these channels to remain open and continue transmitting impulses, leading to paralysis and death of insects. However, insects can develop resistance by changing the shape of the channels themselves.
Previous genetic studies by other scientists, as well as our study, have not found this type of resistance in Anopheles darlingi. Instead, we discovered that resistance develops in a different way: through a set of genes encoding enzymes that break down toxic compounds. High activity of these enzymes, known as P450s, is often responsible for the development of pesticide resistance in other mosquitoes. Since the advent of pesticide use in the mid-20th century, the same set of P450 genes has independently mutated at least seven times in South America.
In French Guiana, another set of P450 genes also showed a similar evolutionary pattern, further confirming the close link between these enzymes and adaptation. Furthermore, when mosquitoes were placed in sealed containers and exposed to pyrethroid insecticides, differences in P450 genes among individual mosquitoes correlated with their survival time.
In South America, large-scale malaria control campaigns using pesticides were only sporadic and may not have been the primary driver of mosquito evolution. Instead, mosquitoes may have been indirectly exposed to agricultural pesticides. Interestingly, we observed the most pronounced signs of evolution in regions with developed agriculture.
Despite the advent of new vaccines and other advances in malaria control in recent years, mosquito control remains key to reducing the spread of malaria.
Several countries are testing genetic engineering to combat malaria. This technology involves genetically modifying mosquito populations to reduce their numbers or reduce their resistance to the malaria parasite. While the mosquitoes’ remarkable adaptability may pose a challenge, the prospects are promising.
My colleagues and I are working to improve methods for detecting emerging pesticide resistance. Genome sequencing remains crucial for detecting new or unexpected evolutionary responses. Adaptive risk is highest under prolonged and intense selective pressure; therefore, minimizing, modifying, and phasing pesticide use can help prevent the development of resistance.
Coordinated monitoring and appropriate responses are essential to combat evolving drug resistance. Unlike evolution, humans are capable of predicting the future.
Jacob A. Tennessen received funding from the National Institutes of Health through the Harvard T.H. Chan School of Public Health and the Broad Institute.
Post time: Apr-21-2026