Malaria Parasite Population Genomics Across Nigeria’s Six Geopolitical Zones: Mapping Genetic Structure, Gene Flow, and Resistance Allele Distribution

National malaria elimination strategies require understanding the genetic structure and gene flow dynamics of P. falciparum parasite populations across geopolitical zones to predict the spread of drug resistance alleles, track transmission chains, and assess the impact of regional control interventions on parasite population connectivity. This doctoral research maps P. falciparum population genomics across Nigeria's six geopolitical zones using whole-genome sequencing of clinical isolates. A systematic multi-site collection was conducted at 12 sentinel sites across the North West, North East, North Central, South West, South East, and South South zones. Eight hundred high-quality isolates collected over two transmission seasons were sequenced on the Illumina HiSeq platform. Population structure analysis using principal component analysis, ADMIXTURE, and identity-by-descent networks characterised genetic differentiation between zones. FST statistics measured pairwise population differentiation, and effective migration surfaces assessed gene flow between zones. Resistance allele frequencies at Pfkelch13, Pfcrt, Pfmdr1, Pfdhfr, and Pfdhps loci were mapped geographically. Temporal allele frequency changes between 2019 and 2024 isolates from resurveyed sites assessed selection dynamics. Evidence from 2020 to 2024 documents significant P. falciparum population structure within sub-Saharan Africa, with implications for zone-specific intervention effects. This study produces the most geographically comprehensive parasite genomic dataset for Nigeria, providing a reference resource for national malaria programme decision-making. Keywords: Plasmodium falciparum, population genomics, gene flow, geopolitical zones, resistance alleles.