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Don't shoot the messenger葉arget their genome
Mosquitoes likely rank at or near the top of everyone's list of least favorite insects for their constant attacks in the warmer months, and they're a key culprit in the spread of disease. One species, Aedes aegypti, is found on six different continents, and is responsible for infecting “more than 400 million people each year with dangerous viral pathogens, including dengue, yellow fever, Zika and chikungunya,” according to a recent Nature article.
The genome of Ae. aegypt was first sequenced in 2007, but given the technological restraints at the time, the resulting genome was piecemeal and disorganized, according to a press release from The Rockefeller University. With only fragments to work with, the help the genome offered was minimal.
In hopes of addressing this issue, Dr. Leslie B. Vosshall, the Robin Chemers Neustein Professor at The Rockefeller University, reached out to fellow researchers around the world in 2016 to create the Aedes Genome Working Group. All told, she brought together 72 coauthors and corporate partners for the effort. A sample of Ae. aegypti DNA was sent to Pacific Biosciences, who was able to provide much longer genetic sequences than those seen in the first 2007 effort. Those sequences were passed along to scientists at Bionano Genomics, who determined how the sequences interlocked, and then to a team at Baylor University, who judged how those sequences were arranged on chromosomes. The collaboration took three years, but at the end of it, the team had “a comprehensive catalog of Ae. aegypti DNA,” notes Rockefeller University. They recently shared their results in the aforementioned Nature piece, titled “Improved reference genome of Aedes aegypti informs arbovirus vector control.”
The researchers made the genome available online a year before formally publishing their results, and it has been a welcome offering, according to Ben Matthews, a research specialist in Vosshall's lab. “Once the genome was publicly available, people started digging into it,” he commented. “Dozens, if not hundreds, of labs have already used it in their work, and that number will only grow with the publication of our paper.”
“In addition to getting the best genome for Ae. aegypti, we’ve also made a roadmap for how to assemble other tricky genomes,” Matthews added. “This study lays out a strategy for taking any organism and turning it into a genetically tractable animal. And I find that really exciting.”
With a solid genome to work off of, the Rockefeller team identified a number of genes, including ones that code for ionotropic receptors, which enable mosquitoes to detect odors—and as such, people. As noted in the paper, “A doubling in the known number of chemosensory ionotropic receptors provides opportunities to link odorants and tastants on human skin to mosquito attraction, a key first step in the development of novel mosquito repellents.” They also discovered that some mosquitoes present with more than one copy of genes that code for glutathione S-transferase (GST), which neutralizes the toxicity of insecticides.
“Increased GST activity has been associated with resistance to multiple classes of insecticides, including organophosphates, pyrethroids and the organochlorine dichlorodiphenyltrichloroethane (DDT)28. Amplification of detoxification genes is one mechanism by which insects can develop insecticide resistance,” the authors explained.
While this could help direct future insecticides at new targets, the team is also looking into de-fanging mosquitoes by altering them genetically. Since only the females of the Ae. aegypti bite and feed on blood—and therefore transmit disease—using the new genome to engineer male-only populations could reduce the spread of diseases.
“To effectively edit the genome of the mosquito, you need to know more than just the sequence of the genes involved,” Matthews stated. “You also need to know the sequence of the surrounding DNA regions, so that you know where to insert the desired genes. And that’s why it’s so important that this new genome is correct and complete.”
In an equally interesting approach, the Rockefeller scientists were able to identify the genes that are responsible for determining a mosquito's susceptibility to dengue virus. If it proves possible to manipulate these genes, populations of mosquitoes that are genetically incapable of being disease carriers could be produced.
"‘Sterile Insect Technique’ and ‘Incompatible Insect Technique’ show great promise to suppress mosquito populations39, but these population suppression methods require that only males are released,” the authors noted in their paper. “A strategy that connects a gene for male determination to a gene drive construct has been proposed to effectively bias the population towards males over multiple generations40, and improved understanding of M locus evolution and the function of its genetic content should facilitate genetic control of mosquitoes that infect many hundreds of millions of people with arboviruses every year1."