Abstract
AbstractSabah, Malaysia, has amongst the highest burden of humanPlasmodium knowlesiinfection in the country, associated with increasing encroachment on the parasite’s macaque host habitat. However, the genomic make-up ofP. knowlesiin Sabah was previously poorly understood. To inform on local patterns of transmission and putative adaptive drivers, we conduct population-level genetic analyses ofP. knowlesihuman infections using 52 new whole genomes from Sabah, Malaysia, in combination with publicly available data. We identify the emergence of distinct geographical subpopulations within the macaque-associated clusters using IBD-based connectivity analysis. Secondly, we report on introgression events between the clusters, which may be linked to differentiation of the subpopulations, and that overlap genes critical for survival in human and mosquito hosts. Using village-level locations fromP. knowlesiinfections, we also identify associations between several introgressed regions and both intact forest perimeter-area ratio and mosquito vector habitat suitability. Our findings provide further evidence of the complex role of changing ecosystems and sympatric macaque hosts in Malaysia driving distinct genetic changes seen inP. knowlesipopulations. Future expanded analyses of evolvingP. knowlesigenetics and environmental drivers of transmission will be important to guide public health surveillance and control strategies.Author SummaryThe zoonoticP. knowlesiparasite is an emerging, yet understudied, cause of malaria in Southeast Asia. Sabah, Malaysia, has amongst the highest burden of human P. knowlesi infection in the country, however, the region is currently understudied. Thus, we produced a collection of high-qualityP. knowlesigenomes from Sabah, and in combination with publicly available data, performed an extensive population genetics analysis. Our work contributes novel insights forPlasmodium knowlesipopulation genetics and genetic epidemiology.
Publisher
Cold Spring Harbor Laboratory