Genomic comparison of chromosome 4 of human Plasmodium species

Abstract Background: Malaria, a devastating disease primarily caused by five Plasmodium species in humans, continues to pose a significant global health challenge, particularly in sub-Saharan Africa. The parasite’s ability to evade the host immune system through antigenic variation is a major obstacle to malaria control. Genes responsible for this variation are concentrated in subtelomeric regions of chromosomes, with chromosome 4 being a notable locus for such genes. This study presents a comparative genomic analysis of chromosome 4 across the five human-infecting Plasmodium species: Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, Plasmodium vivax , and Plasmodium knowlesi . Methodology: The complete nucleotide sequences of chromosome 4 for the five Plasmodium species were retrieved from the National Center for Biotechnology Information GenBank database. We performed a comprehensive bioinformatic analysis to compare their genomic features. This included calculation of GC content and sequence length, de novo gene prediction using AUGUSTUS, functional annotation of predicted genes through Basic Local Alignment Search Tool against the PlasmoDB database, and gene ontology (GO) enrichment analysis. Phylogenetic relationships were inferred using Multiple Alignment using Fast Fourier Transform for multiple sequence alignment and PhyML for maximum likelihood tree construction. Results: Our analysis revealed significant differences in the genomic landscape of chromosome 4 among the five species. P. knowlesi exhibited the highest GC content (39.65%) and gene density, with 192 predicted genes. In contrast, P. ovale had the smallest chromosome 4 and the lowest gene count. Phylogenetic analysis confirmed that the common ancestor of P. falciparum, P. vivax, P. malariae , and P. ovale diverged from the lineage leading to P. knowlesi . We identified a set of conserved genes across all five species, as well as species-specific genes, including some known virulence factors such as the var and rifin gene families in P. falciparum . GO analysis of the predicted genes revealed enrichment for terms related to pathogenesis and immune evasion. Conclusion: This comparative genomic study provides a detailed profile of chromosome 4 in human Plasmodium species, highlighting both conserved and species-specific features. These findings offer valuable insights into the evolutionary dynamics of this chromosome and its role in host–parasite interactions. The identification of species-specific genes and their functional annotation may pave the way for the development of novel, targeted interventions, such as species-specific vaccines and antimalarial drugs.