Skip to main content
Premium Trial:

Request an Annual Quote

Selective Sweep in Malaria-Carrying Mosquitoes in Southern Africa Linked to Insecticide Resistance

NEW YORK (GenomeWeb) – Researchers from the Liverpool School of Tropical Medicine have identified a selective sweep within malaria-transmitting mosquitoes surrounding an allele that confers insecticide resistance.

Liverpool's Charles Wondji and his colleagues analyzed the genomes of Anopheles funestus mosquitoes collected from different parts of Africa, before and after an effort to scale up vector control. While insecticide-treated bed nets, indoor spraying, and other control methods have prevented more than 660 million cases of malaria since 2000, they have also driven mosquitoes to evolve resistance to the commonly used pyrethroid insecticides.

By comparing the An. funestus genomes through microsatellite, whole-genome sequencing, and targeted sequencing analysis, the researchers identified a selective sweep that includes a resistance-associated allele of cytochrome P450 monooxygenase CYP6P9a that is nearly fixed in southern Africa, as they reported today in PLOS Genetics.

"By elucidating patterns of evolution of insecticide resistance in a major African malaria vector following insecticide‐based interventions … this study has shed light on how mosquitoes evolutionarily respond to the massive selection pressure from insecticide‐based control interventions across Africa, and provided vital information to help improve the implementation of successful control strategies," Wondji said in a statement.

The researchers analyzed genetic diversity at 11 microsatellites within the genomes of An. funestus from six African populations: Benin, Cameroon, Ghana, Malawi, Mozambique, and Uganda. Based on this, they noted reduced diversity at the telomeric end of chromosome 2R that was restricted to two markers near the pyrethroid resistance quantitative trait locus (QTL) rp1 and the resistance gene CYP6P9a. The lowest diversity at this marker was observed in the two southern African populations, Malawi and Mozambique, which also have the highest levels of insecticide resistance. To the researchers, this indicated that the low diversity is due to a selective sweep that was driven by efforts to control the mosquito population.

The CYP6P9a allele present in the Malawi and Mozambique populations, which is present in those groups to near fixation, is associated with greater efficiency in metabolizing pyrethroids, the researchers added.

Analysis of the nine neutral markers indicated that the Malawi and Mozambique populations diverged from the other African populations, as well as from each other. The researchers noted that this difference between southern and other African populations suggests that there is a barrier to gene flow between the groups.

A fine-scale polymorphism analysis of the rp1 QTL in An. funestus from Malawi, Mozambique, and the moderately resistant Cameroon population found reduced polymorphisms around CYP6P9a in the Malawi and Mozambique populations, but not the Cameroon population. In addition, sequencing of the CYP6P9a resistance gene in 59 mosquitoes from the six African counties uncovered strong directional selection at this site in Malawi and Mozambique mosquitoes.

The researchers also examined mosquitoes collected in 2002, prior to the expansion of vector control in Malawi and Mozambique. The earlier samples had higher levels of genetic diversity on chromosome 2R. That only this region exhibited a difference in genetic diversity further indicates that the selective sweep is related to the beefing up of vector controls, the researchers said.

Likewise, whole-genome sequencing of mosquitoes collected in Malawi in 2002 and 2014 uncovered changes in allele frequencies between the two time points, and the researchers noted that the most striking loss of diversity surrounded the rp1 locus.

This, the researchers noted in their paper, underscores the risk of relying on one type of insecticide for mosquito control and the need for additional insecticides. "This study highlights the risk that if this level of selection and spread of resistance continues unabated, our ability to control malaria with current interventions will be compromised," Wondji added. "We plan to expand our research into understanding why there is a limited gene flow between African regions of this malaria vector and how it could impact the spread of resistance in the future."