Compositional constraints and selection forces dictate codon usage in human bocavirus

Abstract

Objectives: Human bocavirus (HBoV), of the genus Bocaparvovirus, is a small, non-enveloped linear single-stranded DNA virus of the Parvoviridae family. The virus is known to cause severe life-threatening respiratory tract infections in pediatric patients. Considering its deleterious impacts on respiratory, gastrointestinal, and hematological health, we prompted to investigate codon usage patterns, parity, neutrality, Nc-GC3 analysis, gene expression, Intrinsic codon bias index (ICDI), Codon bias index (CBI), Relative codon deoptimization index (RCDI), Translational selection (P2), and measure independent of length and composition (MILC) to investigate the role of evolutionary constraints such as selection and mutation and molecular patterns present in HBoV. Methods: 805 HBoV sequences were investigated using various software and statistical tools. Results: The present study demonstrated the predominant governance of selection forces over mutational forces in determining codon usage. The compositional parameters were pivotal in deciding the dinucleotide occurrence and frequently used codons. Since the HBoV genomes were A-and T-nucleotide-rich, A/T ending codons and ApAdinucleotides were overrepresented. Despite the A/T richness, at the non-neutral positions of the codon, the G/C nucleotide content was found to be the highest, again underscoring the selective forces that drive a high percentage of G/C nucleotide. At the non-neutral codon positions, with an increase in GC nucleotide, codon bias also increased, while at the third position of the codon, with an increase in GC content, it was decreased. Overall, there is a low codon bias in HBoV. A total of nine A/T ending codons were overrepresented, while nineteen G/C ending codons were underrepresented. Interestingly, instead of CTG, a commonly overrepresented codon, AGA was the most overrepresented codon. AGA and CGG encoding for arginine showed average maximum and minimum RSCU values in the HBoV genome. Conclusions: The collective inference from the neutrality plot, Nc-GC3 curve, and P2 analysis indicated the prevalence of selection force over mutation force. With that, our study offers a novel perspective on the different molecular patterns present in HBoV, and the results might be implicated in designing efficacious therapeutic modalities against HBoV.