Introgression of a synthetic sex ratio distortion system from Anopheles gambiae into Anopheles arabiensis

Abstract

I-PpoI is a homing endonuclease that has a high cleavage activity and specificity for a conserved sequence within the ribosomal rDNA repeats, located in a single cluster on the Anopheles gambiae X chromosome. This property has been exploited to develop a synthetic sex ratio distortion system in this mosquito species. When I-PpoI is expressed from a transgene during spermatogenesis in mosquitoes, the paternal X chromosome is shredded and only Y chromosome-bearing sperm are viable, resulting in a male-biased sex ratio of >95% in the progeny. These distorter male mosquitoes can efficiently suppress caged wild-type populations, providing a powerful tool for vector control strategies. Given that malaria mosquito vectors belong to a species complex comprising at least two major vectors, we investigated whether the sex distorter I-PpoI, originally integrated in the A. gambiae genome, could be transferred via introgression to the sibling vector species Anopheles arabiensis. In compliance with Haldane’s rule, F1 hybrid male sterility is known to occur in all intercrosses among members of the Anopheles gambiae complex. A scheme based on genetic crosses and transgene selection was used to bypass F1 hybrid male sterility and introgress the sex distorter I-PpoI into the A. arabiensis genetic background. Our data suggest that this sex distortion technique can be successfully applied to target A. arabiensis mosquitoes.

Next-generation gene drive for population modification of the malaria vector mosquito, Anopheles gambiae

“…gambiae strain variants and perhaps introgressed into those species that can form fertile hybrids [ An. coluzzii and Anopheles arabiensis ( 32 , 33 )]. However, fertile hybrids are a prerequisite to introgression, so any species showing this reproductive barrier should be immune to the drive.…”

Bionomics of Anopheles arabiensis from Mamfene in KwaZulu-Natal (South Africa): an area of high malaria transmission in the province

“…Therefore, the population structure of these mosquitoes will require further study before a sterile Insect technique (SIT) programme can be implemented. It will require a sex distortion which is male biases for SIT to succeed [31].…”

Adequacy and sufficiency evaluation of existing EFSA guidelines for the molecular characterisation, environmental risk assessment and post‐market environmental monitoring of genetically modified insects containing engineered gene drives

“…Nonetheless, future efforts to exploit randomly generated Y-chromosome docking strains (Bernardini et al, 2014) or even generate new site-specific docking strains on the Y-chromosome using CRISPR-Cas9 (Buchman and Akbari, 2019) may improve functionality of Y-chromosome nucleases and thus the development of engineered X-shredders (Raban et al, 2020). Moreover, X-shredder systems may be adaptable to other organisms (Bernardini et al, 2019;Fasulo et al, 2020), though the development of such technology has been hampered by the inability to express transgenes, under the control of meiotic promoters, from the sexual chromosomes (Bernardini et al, 2019).…”