Analysis of human P[4]G2 rotavirus strains isolated in Brazil reveals codon usage bias and strong compositional constraints.
The Rotavirus genus belongs to the family Reoviridae and its genome consist of 11 segments of double-stranded RNA. Group A rotaviruses (RV-A) are the main etiological agent of acute viral gastroenteritis in infants and young children worldwide. Understanding the extent and causes of biases in codon usage is essential to the understanding of viral evolution. However, the factors shaping synonymous codon usage bias and nucleotide composition in human RV-A are currently unknown. In order to gain insight into these matters, we analyzed the codon usage and base composition constraints on the two genes that codify the two outer capsid proteins (VP4 [VP8*] and VP7) of 58 P[4]G2 RV-A strains isolated in Brazil and investigated the possible key evolutionary determinants of codon usage bias. The results of these studies revealed that the frequencies of codon usage in both RV-A proteins studied are significantly different than the ones used by human cells. In order to observe if similar trends of codon usage are found when RV-A complete genomes are considered, we compare these results with results found using a dataset of 10 reference strains for whom the complete codes of the 11 segments are known. Similar results were obtained using capsid proteins or complete genomes. The general correlations found between the position of each sequence on the first axis generated by correspondence analysis and the relative dinucleotide abundances indicate that codon usage in RV-A can also be strongly influenced by underlying biases in dinucleotide frequencies. CpG and GpC containing codons are markedly suppressed. Thus, the results of this study suggest that RV-A genomic biases are the result of the evolution of genome composition in relation to host adaptation and the ability to escape antiviral cell responses.
Laboratório de Virologia Comparada e Ambiental, Instituto Oswaldo Cruz/FIOCRUZ, Av. Brasil 4365, Manguinhos, Rio de Janeiro, RJ, Brazil.
Mariela Martínez
MM
Gómez
Luis Fernando Lopez
LF
Tort
Eduardo de Mello
Ede M
Volotao
Ricardo
R
Recarey
Gonzalo
G
Moratorio
Héctor
H
Musto
José Paulo G
JP
Leite
Juan
J
Cristina
D000956:Antigens, Viral / Q000235:genetics*; D001482:Base Composition; D001938:Brazil; D036022:Capsid Proteins / Q000235:genetics*; D002675:Child, Preschool; D003062:Codon; D005243:Feces / Q000821:virology; D005814:Genes, Viral; D006801:Humans; D007223:Infant; D015999:Multivariate Analysis; D016366:Open Reading Frames; D012367:RNA, Viral / Q000302:isolation & purification; D012401:Rotavirus / Q000235:genetics*; D017422:Sequence Analysis, DNA; D018709:Statistics, Nonparametric
D000956:Antigens, Viral; D036022:Capsid Proteins; D003062:Codon; D012367:RNA, Viral; C060339:VP4 protein, Rotavirus; C050779:VP7 protein, Rotavirus
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