AsianScientist (Feb. 8, 2022) – An India-US research team has leveraged powerful gene editing technology to replace genes conferring insecticide resistance in fruit flies. Described in Nature Communications, the technique could help reduce insecticide usage and open new avenues for pest control.
Invasive insects destroy about 40 percent of crop production worldwide, costing the global economy at least US$70 billion in losses, annually. Insecticides play a critical role in controlling crop damage in addition to curbing the spread of mosquito-borne diseases like malaria.
Over the years, however, many bugs have developed resistance to these insecticides. Exacerbating the conundrum, the excessive insecticide usage itself induces insect populations to genetically adapt and become less sensitive to these chemical sprays.
Researchers from the Tata Institute for Genetics and Society in India and their international collaborators developed a novel gene editing strategy based on CRISPR/Cas9 technology to restore insects’ native susceptibility to insecticides. They focused on an insect protein called the voltage-gated sodium channel (vgsc) that the insecticide chemicals normally attack. However, when genetic mutations alter the protein’s structure, the insecticide can no longer bind to vgsc, thus conferring resistance.
The researchers also looked into the inheritance of the resistance in the offspring. The baby insects inherit two versions of a gene, one from each parent. To alter the inheritance of these variants, the team engineered an add-on to the CRISPR/Cas9 technology, which cuts the parents’ DNA at specific sites. So, when susceptible and resistant insects mate, the resistant variant is cut out and is replaced with a normal copy of the gene in the offspring’s genetic material. That allows the genetic correction to spread throughout a population, resulting in insects bearing normal vgsc proteins.
As a proof-of-concept, the researchers tested the method on fruit flies, which have well-established genetic models. In a fruit fly population, which had 83 percent resistant flies and 17 percent susceptible flies, the CRISPR/Cas9 strategy eventually reversed the proportion to an 87 percent insecticide-susceptible population within 10 generations.
Such success, the authors said, relies on the method to bias the inheritance of the genetic variants towards selecting the normal copy of the gene. That encourages more of the population to adopt the susceptible form, even if it would result in less fit insects. Otherwise, natural evolutionary forces would keep selecting in favor of the resistant insect variants to increase their survival.
Similar approaches could be explored for other insects like mosquitoes, the researchers highlighted. For example, genes that make mosquitoes susceptible to malaria parasites could be replaced by naturally occurring variants that make them resistant to parasites. With this new toolbox, the team is hopeful that the pests can be effectively controlled using far less insecticides.
“This successful proof-of-principle opens up numerous possibilities, including targeted reversion of insecticide-resistant populations to a susceptible state.” the authors concluded.
The article can be found at: Kaduskar et al. (2022) Reversing insecticide resistance with allelic-drive in Drosophila melanogaster.
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Source: Tata Institute of Genetics and Society; Photo: Keagan Henman/Unsplash.
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