Scientists at Virginia Tech say they have found a new way to identify genetic targets useful for controlling mosquito populations, potentially offering an alternative to insecticides. Their study “Hybridization between Aedes aegypti and Aedes mascarensis mosquitoes leads to disruption of male sex determination,” published in Communications Biology, focused on the genetic basis of species incompatibility.
The team crossed Ae. aegypti, a major global arboviral disease vector, and its sibling species, Ae. mascarensis, from the Indian Ocean. When offspring is crossed back with one parent, about 10 percent of the progeny becomes intersex and is unable to reproduce.
The researchers identified abnormalities in the sex determination pathways of these intersex mosquitoes. They found that these mosquitoes are genetic males but express both male and female genes, leading to mixed physical traits.
By understanding these genetic factors, they hope to develop strategies to create all-male mosquito populations, which could help control mosquito numbers by eliminating females. This research also could help identify genes affecting female mosquito behavior, aiding in future vector control methods.
Significant findings for disease control
These findings are significant for controlling diseases such as Zika and dengue, as better mosquito control can reduce the spread of these diseases.
“Understanding the sex determination pathway and its disruptions in mosquitoes is critical for the effective control of disease vectors through genetic manipulations based on sex separation,” write the investigators. “When male hybrids of Aedes aegypti females and Ae. mascarensis males are backcrossed to Ae. aegypti females, a portion of the backcross progeny manifests as males with abnormal sexual differentiation. We discovered a significant correlation between pupal abnormalities and the feminization of subsequent adults exemplified by the relative abundance of ovarian and testicular tissues. All intersex individuals were genetic males as they expressed a male determining factor, Nix.
“Further, our analysis of the sex-specific splicing of doublesex and fruitless transcripts demonstrated the presence of both male and female splice variants indicating that sex determination is disrupted. A comparative transcriptomic analysis revealed similar expression levels of most female-associated genes in reproductive organs and carcasses between intersexual males and normal females.
“Moreover, intersexes had largely normal gene expression in testes but significant gene downregulation in male accessory glands when compared with normal males. We conclude that evolving hybrid incompatibilities between Ae. aegypti and Ae. mascarensis involve disruption of sex determination and are accompanied by changes in gene expression associated with sexual differentiation.”
Though insecticides have been relatively effective at controlling mosquito populations in the past, they are now being reevaluated as they are significantly decreasing in effectiveness and are not ecologically friendly.
“What we found is that the morphological abnormalities start in the pupal stage during development, and in adults, the most severe cases have both testes and ovaries in one individual, which is very unusual for these species. Now we want to understand what causes these abnormalities.”
The researchers found that intersex mosquitoes express both male and female variants of sex determination genes, leading to mixed morphologies. While female-biased genes are expressed normally in intersexes, male-biased genes show decreased expression in certain male reproductive parts, though testes-related genes remain at normal levels.
The study can aid mosquito control by identifying new sex determination pathway genes to create all-male populations, thereby eliminating females, and reducing vector numbers. Additionally, the identification of sex-specific genes can help develop genetic constructs to manipulate traits in wild populations.
“Since the intersex is genetically male but expresses female transcripts, it provides a system to identify genes affecting female behavior, which can be useful for future vector control strategies,” said Jiangtao Liang, PhD, a postdoctoral associate in entomology. “Intersexes can serve as a valuable model for the discovery of genetic factors involved in sex determination, sexual differentiation, mating, host-seeking, and blood-biting behaviors in mosquitoes. Finding new sex determination pathway genes and their disruptions in mosquitoes will contribute to the effective control of disease vectors through genetic manipulations based on sex separation.”
For diseases such as Zika and dengue, understanding mosquito genetics can lead to better control methods, reducing the spread of disease around the world, according to the scientific team.
