Two of the deadliest mosquitoes have thrived thanks to their ties to humans | Science

The slave trade shows how, at times, history returns to slap the present in the face. Between the 16th and 19th centuries, some 15 million Africans were torn from their homes in a triangle that linked Africa, European traffickers, and the American colonies. Aboard those slave ships also traveled mosquitoes of the species Aedes aegypti.

A groundbreaking study using genetic data from these insects, published in Science, now illustrates how this species — the main vector for dengue, Zika virus, yellow fever, and chikungunya — evolved into a more invasive and harmful version that, centuries later, spread from the Americas to other tropical and subtropical regions of the world. In parallel, another study — also published in the same scientific journal — shows how Anopheles funestus, one of the lesser-known yet most dangerous malaria vectors, developed resistance to insecticides as early as the 1960s.

A team of about 30 scientists, using modern sequencing techniques, has mapped the complete genome of 1,206 A. aegypti mosquitoes from 73 populations worldwide. With this wealth of information, they were able to reconstruct the genealogical tree and historical evolution of the species, which now lives in proximity to 4 billion people and, according to the World Health Organization, infects 390 million annually with dengue alone. Yet, not long ago in evolutionary terms, this dark-colored mosquito with white markings did not leave the jungles nor had it developed an appetite for human blood.

A. aegypti emerged on the islands of the western Indian Ocean, entered Africa, spread there, and from there reached the Americas with the voyages of European discovery,” summarizes Andrea Gloria-Soria, an evolutionary biologist at the Center for Vector Biology and Zoonotic Diseases at the Connecticut Agricultural Experiment Station in the United States, who co-authored the first study published in Science.

Delving into their origin, genetics shows that those first mosquitoes lived in the jungle and fed on the blood of reptiles and small mammals. About 5,000 years ago, they had already spread throughout sub-Saharan Africa, and it was in the southern edge of the desert — lacking shelter and other food sources — they survived in wells and oases. Since then, they tied their fate to humans.

Gloria-Soria continues the account of this history that has so deeply marked humanity: “What we didn’t know until now is how this transition happened, because two forms of A. aegypti emerged: the wild and the domestic, both hematophagous [blood-feeding]. But the wild form is a generalist that feeds on a variety of mammals and is found exclusively in Africa and the islands of the Indian Ocean. The form found on other continents is the domestic type, specialized in humans and with a tendency to reproduce near human populations.” The latter is the invasive form, responsible for most cases of dengue.

By comparing the genomes of different populations, the scientists were able to see that specialization in humans must have begun in Africa, but it was their arrival in the Americas, via the slave trade, that set in motion what would become a major public health threat. “The most important point of this work is that the invasive form appeared in the Americas. Exactly how remains to be investigated, but our data suggest that the differences we found are related to dietary habits and pathogen defenses that were not the same as those that existed in Africa,” says Gloria-Soria.

He colleague Jacob Crawford, from Debug — a vector-control research unit of Alphabet, Google’s parent company — and co-author of the study, recalls that outbreaks of yellow fever and dengue were already recorded in the Americas as early as the 17th century. “It therefore seems likely that the expansion of Aedes aegypti populations in the Americas triggered disease outbreaks a century after their arrival through the slave trade,” he explains in an email.

Genetic data also reveal how, from the late 19th century until the mid-20th, there was a radical narrowing in the species’ variability. Those were the decades when many countries strengthened public health and surveillance systems, almost eradicating one of the world’s most disease-transmitting insects. “A. aegypti caused major yellow fever outbreaks in Spain in the 19th century. They eradicated it through the use of insecticides and the reduction of larval habitat, which was achieved by modernizing plumbing and sanitation systems,” says Crawford. Similar campaigns minimized the insect’s distribution.

In 1952, there was an outbreak of dengue fever in the territory of Tanganyika, which was then a British colony, and now is part of Tanzania. The vectors were not genetically African mosquitoes, but rather mosquitoes related to the American mosquitos. A. aegypti had returned to Africa, but in its most invasive form. Since then, outbreaks have continued to spread.

“The recent return is mainly due to frequent reintroductions resulting from increased globalization and urbanization. This invasive mosquito is perfectly adapted to the urban environment and thrives in cities,” explains Crawford, who warns: “It is clear that Aedes aegypti has the potential to re-invade much of temperate and subtropical Europe, as we have seen with its recent establishment in Cyprus and Madeira.” And also in Spain’s Canary Islands.

The lesser-known malaria vector

Science also published a study on another mosquito, often overlooked, yet potentially an even more dangerous malaria vector than members of the so-called Anopheles gambiae complex — a group of species so morphologically similar that they are often treated as one. Its name is telling: Anopheles funestus.

An. funestus is one of the four main vectors of malaria in sub-Saharan Africa, where 94% of malaria cases occur [causing half a million deaths a year]. The other three main vector species are all members of the Gambiae Complex,” says Marilou Boddé, a researcher at the Pasteur Institute in Madagascar and first author of the study, in an email. “In much of eastern and southern Africa, it is, in fact, the species that most frequently transmits malaria,” adds Boddé, who conducted this study while at the Wellcome Sanger Institute. Until now, most of the research had been done on other malaria-causing mosquitoes.

This new research sequenced the genomes of more than 600 An. funestus mosquitoes captured between 2014 and 2018. To observe their historical evolution, the researchers compared their genomes with the genetic data of another 45 recovered from museums — the oldest dating back to 1927 and the most recent to 1967. This allowed the team to see the species’ evolutionary patterns. One of those patterns was the emergence of resistance.

“Almost as soon as insecticides began to be used on a large scale — for example, in national insecticide spraying campaigns or, more recently, in the distribution of large quantities of insecticide-treated bed nets — mosquitoes began to develop resistance,” says Boddé.

The scientists observed DNA changes that neutralize the harmful effects of insecticides. “Mosquitoes with these mutations have a selective advantage over mosquitoes without them, since for them, contact with insecticides is often fatal,” the researcher adds.

The work also identifies the genes most susceptible to genetic modification using modern techniques that would favor certain traits that, in the long run, would compromise the survival of Anopheles funestus. This technology is already being researched to eradicate, at least locally, other harmful mosquitoes.

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