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Identification of complex Plasmodium falciparum genetic backgrounds circulating in Africa: a multicountry genomic epidemiology analysis
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International audience. Background: The population structure of the malaria parasite Plasmodium falciparum can reveal underlying adaptive evolutionary processes. Selective pressures to maintain complex genetic backgrounds can encourage inbreeding, producing distinct parasite clusters identifiable by population structure analyses.Methods: We analysed population structure in 3783 P falciparum genomes from 21 countries across Africa, provided by the MalariaGEN Pf7 dataset. We used Principal Coordinate Analysis to cluster parasites, identity by descent (IBD) methods to identify genomic regions shared by cluster members, and linkage analyses to establish their co-inheritance patterns. Structural variants were reconstructed by de novo assembly and verified by long-read sequencing.Findings: We identified a strongly differentiated cluster of parasites, named AF1, comprising 47 (1·2%) of 3783 samples analysed, distributed over 13 countries across Africa, at locations over 7000 km apart. Members of this cluster share a complex genetic background, consisting of up to 23 loci harbouring many highly differentiated variants, rarely observed outside the cluster. IBD analyses revealed common ancestry at these loci, irrespective of sampling location. Outside the shared loci, however, AF1 members appear to outbreed with sympatric parasites. The AF1 differentiated variants comprise structural variations, including a gene conversion involving the dblmsp and dblmsp2 genes, and numerous single nucleotide polymorphisms. Several of the genes harbouring these mutations are functionally related, often involved in interactions with red blood cells including invasion, egress, and erythrocyte antigen export.Interpretation: We propose that AF1 parasites have adapted to some unidentified evolutionary niche, probably involving interactions with host erythrocytes. This adaptation involves a complex compendium of interacting variants that are rarely observed in Africa, which remains mostly intact despite recombination events. The term cryptotype was used to describe a common background interspersed with genomic regions of local origin.
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