Reduced Genetic Diversity of Key Fertility and Vector Competency Related Genes in s.l. Across Sub-Saharan Africa.

BACKGROUND

Insecticide resistance challenges the vector control efforts towards malaria elimination and proving the development of complementary tools. Targeting the genes that are involved in mosquito fertility and susceptibility to with small molecule inhibitors has been a promising alternative to curb the vector population and drive the transmission down. However, such an approach would require a comprehensive knowledge of the genetic diversity of the targeted genes to ensure the broad efficacy of new tools across the natural vector populations.

METHODS

Four fertility and parasite susceptibility genes were identified from a systematic review of the literature. The Single Nucleotide Polymorphisms (SNPs) found within the regions spanned by these four genes, genotyped across 2784 wild-caught s.l. from 19 sub-Saharan African (SSA) countries, were extracted from the whole genome SNP data of the Ag1000G project (Ag3.0). The population genetic analysis on gene-specific data included the determination of the population structure, estimation of the differentiation level between the populations, evaluation of the linkage between the non-synonymous SNPs (nsSNPs), and a few statistical tests.

RESULTS

As potential targets for small molecule inhibitors to reduce malaria transmission, our set of four genes associated with fertility and their susceptibility to comprises the mating-induced stimulator of oogenesis protein (, AGAP002620), (, AGAP004203), (, AGAP001826), and (, AGAP013327). The analyses performed on these potential targets of small inhibitor molecules revealed that the genes are conserved within SSA populations of s.l. The overall low Fst values and low clustering of principal component analysis between species indicated low genetic differentiation at all the genes ( and ). The low nucleotide diversity (>0.10), negative Tajima's D values, and heterozygosity analysis provided ecological insights into the purifying selection that acts to remove deleterious mutations, maintaining genetic diversity at low levels within the populations. None of nsSNPs were identified in linkage disequilibrium, whereas a few weakly linked nsSNPs with ambiguous haplotyping were detected at other genes.

CONCLUSIONS

This integrated finding on the genetic features of major malaria vectors' biological factors across natural populations offer new insights for developing sustainable malaria control tools. These loci were reasonably conserved, allowing for the design of effective targeting with small molecule inhibitors towards controlling vector populations and lowering global malaria transmission.