What question did this study set out to answer?

This research aims to assess the genetic diversity and evolutionary dynamics of the Pfs230 gene to evaluate its potential as a malaria transmission-blocking vaccine candidate.

June 3, 2026Malaria Journal0 citationsOpen Access

Genetic diversity of the Plasmodium falciparum Pfs230 gene in four East African countries supports its potential as a malaria transmission‑blocking vaccine candidate

AKAngelina J. KisambaleIfakara Health Institute RMRamadhan MoshiUniversity of Nairobi DPDativa PereusIfakara Health Institute

Key Points

This research aims to assess the genetic diversity and evolutionary dynamics of the Pfs230 gene to evaluate its potential as a malaria transmission-blocking vaccine candidate.
Utilized genomic data from the MalariaGEN Pf7 database with samples from Ethiopia, Kenya, Tanzania, and Uganda.
Computed genetic metrics including nucleotide diversity, haplotype diversity, Tajima’s D, and Wright’s fixation index (FST).
Analyzed 1,471 sequences, retaining 1,312 after quality filtering for downstream analysis.
Overall nucleotide diversity of the Pfs230 gene was low (π = 5.9 × 10-4) across the four countries.
Haplotype diversity (Hd) was high at 0.999 with 496 haplotypes across 718 monoclonal sequences.
Negative Tajima's D values in all countries indicate low genetic variability, significantly lower in Kenya (−2.131; P < 0.01) and Tanzania (−2.056; P < 0.05).

Abstract

The current wide-spread drug and insecticide resistance in malaria parasites and mosquito vectors reinforces the urgent need of innovative interventions such as stage-specific vaccines. Transmission-blocking vaccine (TBV) candidates, including Plasmodium falciparum Pfs48/45 and Pfs230 play an essential role in enabling parasite fertilization within mosquitoes. This study evaluated the genetic diversity and evolutionary dynamics of the Pfs230 gene to provide critical information on its potential as a suitable TBV candidate. The study utilized genomic data from the MalariaGEN Pf7 database, which included samples collected from four East African countries: Ethiopia, Kenya, Tanzania, and Uganda. Genetic metrics including nucleotide diversity, haplotype diversity (Hd), Tajima’s D, and Wright’s fixation index (FST) were computed to characterize the genetic diversity of the Pfs230 gene. Of the 1471 sequences retrieved, 1312 passed quality filtering and were retained for downstream analysis. Overall, nucleotide diversity of the Pfs230 gene was low across the four countries (π = 5.9 × 10-4). The Hd was 0.999 with 496 haplotypes among 718 monoclonal sequences, and 8.1% (n = 40) of the haplotypes were shared between two or more populations. The overall non-synonymous to synonymous substitution ratio was 0.43, and the Tajima’s D values were negative in all countries, with statistically significant lower values in Kenya (− 2.131; P 0.10) and Uganda (− 0.096; P > 0.10) had relatively higher values. Principal component analysis (PCA) and Wright's fixation index (FST) did not show any population differentiation. Similarly, the phylogenetic analysis indicated limited sequence divergence among populations. Low levels of genetic diversity and differentiation in the parasite populations was observed across the four countries suggesting that the Pfs230 gene is highly conserved, supporting its potential as a promising TBV candidate. Future studies focusing on Pfs230, alongside other key TBV targets will be essential for strengthening evidence-based needs to prioritize and incorporate this gene in the search for malaria vaccines with a broader protection against different parasite stages.

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