Genome Variability and Capsid Structural Constraints of Hepatitis A Virus

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Abstract
The number of synonymous mutations per synonymous site (Ks), the number of nonsynonymous mutations per nonsynonymous site (Ka), and the codon usage statistic (Nc) were calculated for several hepatitis A virus (HAV) isolates. While Ks was similar to those of poliovirus (PV) and foot-and-mouth disease virus (FMDV), Ka was 1 order of magnitude lower. The Nc parameter provides information on codon usage bias and decreases when bias increases. The Nc value in HAV was about 38, while in PV and FMDV, it was about 53. The emergence of 22 rare codons in front of 8 in PV and 7 in FMDV was detected. Most of the conserved rare codons of the P1 region were strategically located at the carboxy borders of β barrels and α helices, their potential function being the assurance of proper folding of the capsid proteins through a decrease in the translation speed. This strategic location was not observed for amino acids encoded by the conserved rare codons of the 3D region. The percentage of bases with low pairing number values was higher in the latter region, suggesting a role of the conserved rare codons in the maintenance of RNA structure. Many of the rare codons in HAV are among the most frequent in humans, unlike in PV or in FMDV. This fact may be explained by the lack of cellular shutoff in HAV. One hypothesis is that HAV has evolved in order to avoid competition with its host for cellular tRNAs.