Comprehensive genomic study of Plasmodium falciparum in Sierra leone: genetic variation and resistance patterns

Abstract

Background: Malaria remains a significant global health concern, with Plasmodium falciparum being the most dangerous of the malaria-causing parasites. Sierra Leone, with year-round transmission of malaria, continues to experience high infection rates, largely due to P. falciparum. Although genomic databases have provided valuable insights into malaria transmission patterns, drug resistance, and population structure, data from Sierra Leone has been limited. This study aims to build on our previous report by incorporating new samples and providing a more comprehensive genomic analysis of P. falciparum in Sierra Leone, with a particular focus on genetic diversity, population structure, and drug resistance.

Methods: We collected P. falciparum samples from Freetown, Sierra Leone, between December 2022 and March 2023. A total of 35 samples underwent sequencing using the MGISEQ and Illumina platforms, resulting in high-coverage genomic data. Population structure was assessed using PCA, NJ trees, and STRUCTURE analysis, alongside comparisons with a global dataset from the pf3k project. Genetic diversity was evaluated using metrics such as , _ω, Tajima’s D, and iHS. XPEHH was used to examine selection pressures across different regions.

Results: Sequencing yielded over 376,450 high-quality SNPs across 35 Sierra Leone isolates, indicating substantial genetic variability. PCA, NJ trees, and STRUCTURE analysis revealed that the Sierra Leone isolates formed distinct clusters from both West African and Southeast Asian samples, with evidence of region-specific genetic adaptation. The low IBD we found suggested that infections were largely independent. Meanwhile the Tajima’s D and iHS analysis showed strong directional selection in genes associated with immune evasion and drug resistance genes, exhibiting ongoing evolutionary pressure due to therapeutic behavior.

Conclusion: This study provides us not only a genomic database but also a profile of P. falciparum in Sierra Leone, revealing high genetic diversity, strong selection pressure on drug resistance genes, and unique population structures. Our data emphasize the need for continued genomic surveillance to better manage malaria.

Supplementary Information: The online version contains supplementary material available at 10.1186/s12864-025-11771-y.

Keywords: Drug resistance; Genomic diversity; Plasmodium falciparum; Population structure; Sierra Leone.

Fig. 1

Comparison of SNP Abundance and Nucleotide Diversity (π) Across Populations in Africa and Asia. A Total SNP counts for individual countries across Africa and Asia, showing variation in genetic diversity across regions. B Mean nucleotide diversity (π) for 5,600 genes in three population groups: Asia, West Africa, and Sierra Leone. The Sierra Leone group demonstrates higher mean nucleotide diversity, consistent with complex population dynamics and local selection pressures

Fig. 2

Structure and Phylogenetic Relationships of P. falciparum Samples from Sierra Leone and Reference Populations. A PCA of Sierra Leone and reference populations from West Africa and Southeast Asia, based on F1 and F2 axes, showing clear separation between African and Asian populations. Sierra Leone samples (open circles) cluster separately, indicating a distinct genetic profile. B PCA plot highlighting F2 and F3 axes, further distinguishing Sierra Leone samples from reference. C ML-tree based on genome-wide SNP data, illustrating the genetic diversity across samples. Sierra Leone samples (open circles) form a separate cluster but show higher genetic diversity. D STRUCTURE analysis showing genetic ancestry inferred from K = 5. Sierra Leone samples exhibit unique genetic ancestry components, distinct from reference. The West African populations show greater genetic diversity with more mixed ancestry, while Southeast Asian populations cluster into fewer distinct genetic components

Fig. 3

Analysis of Identity-by-Descent (IBD) in P. falciparum Samples from Sierra Leone. A Distribution of IBD fraction across 595 sample pairs from Sierra Leone. The vast majority of sample pairs have an IBD fraction below 0.1, indicating low relatedness between infections, with only 1 pair (0.17%) exceeding 0.5. This suggests that most infections are independently acquired, reflecting high transmission and low genetic relatedness among the parasite population in Sierra Leone. B Distribution of highly conserved IBD segments across the 14 chromosomes, showing the number of IBD segments identified in genes associated with immune evasion, including var, rifin, and stevor. Notably, only 188 genes contained highly conserved segments that appeared more than 50 times, primarily concentrated in genes related to immune evasion, indicating the functional importance of these gene families in the population

Fig. 4

Selection Pressure Analysis of P. falciparum Genes from Sierra Leone Isolates. A Tajima’s D values calculated across 5,600 genes from isolates in Sierra Leone, highlighting directional selection on several key loci, including drug resistance genes such as dhfr and cPheRS, and immune evasion genes (var, rifin, stevor). Negative Tajima’s D values across many genes suggest the influence of directional selection. B Comparative analysis of Tajima’s D values between Sierra Leone and West African isolates. While most genes cluster around neutral evolution, drug resistance genes and some surface antigen families show stronger selection pressures in Sierra Leone. C iHS analysis of Sierra Leone samples identifies strong selection signals, particularly in immune evasion gene families and drug resistance loci. The higher iHS scores reflect recent positive selection on these loci. D Rsb analysis between Sierra Leone and Asian populations showed distinct selection patterns between regions, with the Sierra Leone population exhibiting widespread selection signals across genes related to immune evasion and drug resistance