Even while malaria parasites develop resistance to drugs, and malaria-carrying mosquitoes develop resistance to insecticides, scientists hope to suppress and even eradicate these disease-spreading scourges. Scientists are particularly interested in an approach to malaria control that would skew the sex ratios of mosquito populations. If reproduction could be skewed to males, mosquito populations might collapse.
To date, attempts to distort populations toward the reproduction of males have had mixed success. One approach, however, seems especially promising, now that scientists have succeeded in modifying mosquitoes to produce sperm that will create only males.
In a study published June 10 the journal Nature Communications, in an article entitled “A synthetic sex ratio distortion system for the control of the human malaria mosquito,” scientists from Imperial College London have tested a new genetic method that distorts the sex ratio of Anopheles gambiae mosquitoes, the main transmitters of the malaria parasite, so that the female mosquitoes that bite and pass the disease to humans are no longer produced.
“Here we generate a synthetic sex distortion system by exploiting the specificity of the homing endonuclease I-PpoI, which is able to selectively cleave ribosomal gene sequences of the malaria vector Anopheles gambiae that are located exclusively on the mosquito’s X chromosome,” the authors wrote. “We combine structure-based protein engineering and molecular genetics to restrict the activity of the potentially toxic endonuclease to spermatogenesis.”
Shredding of the paternal X chromosome prevents it from being transmitted to the next generation. In the first laboratory tests, the method created a fully fertile mosquito strain that produced 95% male offspring.
The scientists introduced the genetically modified mosquitoes to five caged wild-type mosquito populations. In four of the five cages, this eliminated the entire population within six generations because of the lack of females. The hope is that if this could be replicated in the wild, this would ultimately cause the malaria-carrying mosquito population to crash.
“As with any other forms of pest control, it is important to consider possible pathways for the evolution of resistance. The universal conservation of the I-PpoI recognition sequence within the multicopy essential 28S rDNA locus of animals makes the rapid selection of target site resistance unlikely,” the authors explained. “Other rDNA sequences or alternative X-specific sequence repeats could also be targeted—for example, by recently described programmable DNA endonucleases. Our findings thus suggest a more universal approach toward achieving sex distortion.”
Co-lead researcher Professor Andrea Crisanti said, “For the very first time, we have been able to inhibit the production of female offspring in the laboratory, and this provides a new means to eliminate the disease.” The other co-lead researcher, Nikolai Windbichler, Ph.D., added, “What is most promising about our results is that they are self-sustaining. Once modified mosquitoes are introduced, males will start to produce mainly sons, and their sons will do the same, so essentially the mosquitoes carry out the work for us.”
