Evolutionary mechanisms of adaptation to malaria are understudied in Asian endemic regions despite a high prevalence of malaria in the region. In our research, we performed a genome-wide screening for footprints of natural selection against malaria by comparing eight Asian population groups from malaria-endemic regions with two non-endemic population groups from Europe and Mongolia. We identified 285 adaptive genes showing robust selection signals across three statistical methods, iHS, XP-EHH, and PBS. Interestingly, most of the identified genes (82%) were found to be under selection in a single population group, while adaptive genes shared across populations were rare. This is likely due to the independent adaptation history in different endemic populations. The gene ontology (GO) analysis for the 285 adaptive genes highlighted their functional processes linked to neuronal organizations or nervous system development. These genes could be related to cerebral malaria and may reduce the inflammatory response and the severity of malaria symptoms. Remarkably, our novel population genomic approach identified population-specific adaptive genes potentially against malaria infection without the need for patient samples or individual medical records.
Keywords: Malaria; adaptive genes; cerebral malaria; infectious disease; natural selection; nervous system.