New research from the Debug project reveals the origin and movement of the mosquito Aedes aegypti—which could help disease control efforts
Authors: Dr. Jacob Crawford, Staff Scientist, Debug Dr. Bradley White, Director, Debug
The Global Dengue Threat
More than 4 billion people—half of the world’s population—are at risk of contracting dengue, a mosquito-transmitted disease, each year. And global cases are surging: according to the World Health Organization, reported instances of dengue have increased eight-fold in the past 25 years, from 500,000 in 2000 to a historic high of more than 14.6 million in 2024. Severe dengue can wreak havoc on the human body, causing sickness and even death.
While more than 3,500 species of mosquito exist, the Aedes aegypti mosquito is responsible for almost all cases of dengue. Unfortunately, there is no available vaccine that can provide comprehensive protection from the disease. As a result, the only way to limit transmission of dengue and other viral diseases transmitted by this mosquito species, including Zika and chikungunya, is by controlling the Aedes aegypti population itself.
The Debug team and academic colleagues spent the past several years putting together the first comprehensive genomic database that helps to catalogue the history of Aedes aegypti migration across the world and the genetic mutations that occurred along the way. These findings represent a major advancement in our knowledge of Aedes aegypti genomics and our mission of eliminating disease-carrying mosquitoes: providing a platform for both optimizing the implementation of existing vector controls tools and developing novel interventions.
We recently published our research in Science, along with the datasets we used to inform our work, in the hopes that other people working on controlling mosquito-borne illnesses may also benefit from these discoveries.
From the Forest to the City
Historically, Aedes aegypti was only found in African forests, breeding in tree-holes and feeding on non-human primates and other animals. While these forest populations still exist, over the past 500 years, a form of Aedes aegypti has adapted to specialize on humans—breeding in artificial water sources and feeding nearly exclusively on people. The human-specialized form has invaded almost the entirety of the tropical and subtropical world, with more recent incursions into temperate areas as well.
An organism’s genome can serve as a historical record of sorts, showing, for example, when a species’ population size may have changed and documenting migration patterns. In order to better understand the history of Aedes aegypti invasion, we sequenced the genomes of 1,206 individual mosquitoes from 73 locations across every continent except Antarctica, including both animal-preferring and invasive, human-preferring populations.
To collect some of the samples, our colleagues set up oviposition cups (i.e. artificial containers holding water) across forests and cities and waited for mosquitoes to lay eggs in the water. Because it’s impossible to identify eggs in the field, our colleagues brought all the eggs they gathered back to the lab for molecular testing.
Debug collaborators Dr. Noah Rose (UC San Diego) and Gilbert Bianquinche collecting Aedes aegypti eggs in Senegal for the study.
The team then sequenced the DNA of these mosquitoes on the Illumina platform and used Google Cloud’s compute power to map the billions of sequencing reads to the genomes of these mosquitoes, identifying millions of common and rare mutations. Demographic analyses based on this mutation database allowed us to pinpoint which regions of the genome were shared between populations, helping to unravel the routes that Aedes aegypti traveled as it invaded the globe and the approximate dates of these migrations.
Mastering Mosquitoes’ Movements
We found over 141 million mutations in these genomes that tell us about how Aedes aegypti has changed and moved over time.
We discovered strong evidence, in agreement with historical records on disease occurrence, that this species of mosquito migrated from Africa to the Americas \~350 years ago, almost certainly on ships carrying enslaved people. Approximately 100 years after this migration, the American population of the Aedes aegypti exploded in size and rapidly invaded the rest of the tropical world—including the Mediterranean basin, Asia, and Australia.
We also found strong evidence that this invasive form of Aedes aegypti has returned to Africa, helping to explain the recent, unprecedented urban dengue outbreaks in the region. These “back-to-Africa” populations harbor insecticide resistance genes selected for outside the continent, making control of the mosquitoes all the more difficult.
The Implications for Global Health
The Debug project is developing novel technology, powered by artificial intelligence, to raise and release sterile male mosquitoes in order to decrease populations of the ones that carry disease. This recent body of research has the potential to help us accelerate the process of introducing sterile Aedes aegypti into the regions that most urgently need population suppression.
Adult Aedes aegypti mosquitoes in a Debug cage being prepared for backcrossing
Whenever we release sterile males into a new area, it can take up to nine months to backcross our sterile lines with locally caught mosquitoes to ensure we are releasing Aedes aegypti that genetically matches the local population. The new dataset helps us to determine over what geographic region a single genetic line can be released - for example, our research found the same genetic line of the species could be released across multiple countries in South East Asia - which allows us to begin releases quicker and make the sterile male manufacturing process more efficient. We hope that by publicly releasing our dataset, we can provide a unique platform for researchers to develop new tools in the ongoing fight against dengue, Zika, and other illnesses spread by Aedes aegypti.
As we continue to develop technologies and methods to target disease-carrying mosquitoes, we’re partnering closely with scientists, communities, and governments around the world. If you’re interested in collaborating with our team, please reach out to partners@debug.com
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