Comparative analysis of codon usage patterns of Plasmodium helical interspersed subtelomeric (PHIST) proteins

Background: Plasmodium falciparum is a protozoan parasite that causes the most severe form of malaria in humans worldwide, which is predominantly found in sub-Saharan Africa, where it is responsible for the majority of malaria-related deaths. Plasmodium helical interspersed subtelomeric (PHIST) proteins are a family of proteins, with a conserved PHIST domain, which are typically located at the subtelomeric regions of the Plasmodium falciparum chromosomes and play crucial roles in the interaction between the parasite and its human host, such as cytoadherence, immune evasion, and host cell remodeling. However, the specific utilization of synonymous codons by PHIST proteins in Plasmodium falciparum is still unknown.

Methods: Codon usage bias (CUB) refers to the unequal usage of synonymous codons during translation, resulting in over- or underrepresentation of certain nucleotide patterns. This imbalance in CUB can impact various cellular processes, including protein expression levels and genetic variation. To investigate this, the CUB of 88 PHIST protein coding sequences (CDSs) from 5 subgroups were analyzed in this study.

Results: The results showed that both codon base composition and relative synonymous codon usage (RSCU) analysis identified a higher occurrence of AT-ended codons (AGA and UUA) in PHIST proteins of Plasmodium falciparum. The average effective number of codons (ENC) for these PHIST proteins was 36.69, indicating a weak codon preference among them, as it was greater than 35. Additionally, the correlation analysis among codon base composition (GC1, GC2, GC3, GCs), codon adaptation index (CAI), codon bias index (CBI), frequency of optimal codons (FOP), ENC, general average hydropathicity (GRAVY), aromaticity (AROMO), length of synonymous codons (L_sym), and length of amino acids (L_aa) revealed the influence of base composition and codon usage indices on codon usage bias, with GC1 having a significant impact in this study. Furthermore, the neutrality plot analysis, PR2-bias plot analysis, and ENC-GC3 plot analysis provided additional evidence that natural selection plays a crucial role in determining codon bias in PHIST proteins.

Conclusion: In conclusion, this study has enhanced our understanding of the characteristics of codon usage and genetic evolution in PHIST proteins, thereby providing data foundation for further research on antimalarial drugs or vaccines.