Analysis of the Genetic Variation of the Fruitless Gene within the Anopheles gambiae (Diptera: Culicidae) Complex Populations in Africa

SIMPLE SUMMARY: In this study, we have characterized the genetic variation of the Fruitless gene (X: 1283016-1373662) within 18 populations of An. gambiae s.l in Africa. The variant density and the nucleotide diversity were low in the exonic regions of the fru gene, especially the male sex-specific region, the BTB-exons 1 and 2, and the zinc-finger B and C exons. These regions also showed high conservation scores. The allelic frequencies of the non-synonymous SNPs were low (freq < 0.26), except for two SNPs identified at high frequencies (freq > 0.8) in the zinc-finger A and B protein domains. These results showed a low genetic variation overall in the exonic regions of the fru gene, especially the male sex-specific exon and the BTB-exon 1. These findings are crucial for the development of a gene drive construct targeting the fru gene that can rapidly spread without encountering resistance in wild populations. ABSTRACT: Targeting genes involved in sexual determinism, for vector or pest control purposes, requires a better understanding of their polymorphism in natural populations in order to ensure a rapid spread of the construct. By using genomic data from An. gambiae s.l., we analyzed the genetic variation and the conservation score of the fru gene in 18 natural populations across Africa. A total of 34,339 SNPs were identified, including 3.11% non-synonymous segregating sites. Overall, the nucleotide diversity was low, and the Tajima’s D neutrality test was negative, indicating an excess of low frequency SNPs in the fru gene. The allelic frequencies of the non-synonymous SNPs were low (freq < 0.26), except for two SNPs identified at high frequencies (freq > 0.8) in the zinc-finger A and B protein domains. The conservation score was variable throughout the fru gene, with maximum values in the exonic regions compared to the intronic regions. These results showed a low genetic variation overall in the exonic regions, especially the male sex-specific exon and the BTB-exon 1 of the fru gene. These findings will facilitate the development of an effective gene drive construct targeting the fru gene that can rapidly spread without encountering resistance in wild populations.