Analysis of codon usage and nucleotide composition bias in polioviruses

Virology Journal, Mar 2011

Background Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and a member of the family of Picornaviridae and among the most rapidly evolving viruses known. Analysis of codon usage can reveal much about the molecular evolution of the viruses. However, little information about synonymous codon usage pattern of polioviruses genome has been acquired to date. Methods The relative synonymous codon usage (RSCU) values, effective number of codon (ENC) values, nucleotide contents and dinucleotides were investigated and a comparative analysis of codon usage pattern for open reading frames (ORFs) among 48 polioviruses isolates including 31 of genotype 1, 13 of genotype 2 and 4 of genotype 3. Results The result shows that the overall extent of codon usage bias in poliovirus samples is low (mean ENC = 53.754 > 40). The general correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in those polioviruses. Depending on the RSCU data, it was found that there was a significant variation in bias of codon usage among three genotypes. Geographic factor also has some effect on the codon usage pattern (exists in the genotype-1 of polioviruses). No significant effect in gene length or vaccine derived polioviruses (DVPVs), wild viruses and live attenuated virus was observed on the variations of synonymous codon usage in the virus genes. The relative abundance of dinucleotide (CpG) in the ORFs of polioviruses are far below expected values especially in DVPVs and attenuated virus of polioviruses genotype 1. Conclusion The information from this study may not only have theoretical value in understanding poliovirus evolution, especially for DVPVs genotype 1, but also have potential value for the development of poliovirus vaccines.

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Analysis of codon usage and nucleotide composition bias in polioviruses

Jie Zhang 0 Meng Wang 0 Wen-qian Liu 0 Jian-hua Zhou 0 Hao-tai Chen 0 Li-na Ma 0 Yao-zhong Ding 0 Yuan-xing Gu 0 Yong-sheng Liu 0 0 State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences , Lanzhou, 730046 Gansu , China Background: Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and a member of the family of Picornaviridae and among the most rapidly evolving viruses known. Analysis of codon usage can reveal much about the molecular evolution of the viruses. However, little information about synonymous codon usage pattern of polioviruses genome has been acquired to date. Methods: The relative synonymous codon usage (RSCU) values, effective number of codon (ENC) values, nucleotide contents and dinucleotides were investigated and a comparative analysis of codon usage pattern for open reading frames (ORFs) among 48 polioviruses isolates including 31 of genotype 1, 13 of genotype 2 and 4 of genotype 3. Results: The result shows that the overall extent of codon usage bias in poliovirus samples is low (mean ENC = 53.754 > 40). The general correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in those polioviruses. Depending on the RSCU data, it was found that there was a significant variation in bias of codon usage among three genotypes. Geographic factor also has some effect on the codon usage pattern (exists in the genotype-1 of polioviruses). No significant effect in gene length or vaccine derived polioviruses (DVPVs), wild viruses and live attenuated virus was observed on the variations of synonymous codon usage in the virus genes. The relative abundance of dinucleotide (CpG) in the ORFs of polioviruses are far below expected values especially in DVPVs and attenuated virus of polioviruses genotype 1. Conclusion: The information from this study may not only have theoretical value in understanding poliovirus evolution, especially for DVPVs genotype 1, but also have potential value for the development of poliovirus vaccines. - Background When molecular sequence data started to be accumulated nearly 20 years ago, it was noted that synonymous codons are not used equally in different genomes, even in different genes of the same genome [1-3]. As an important evolutionary phenomenon, it is well known that synonymous codon usage bias exists in a wide range of biological systems from prokaryotes to eukaryotes [4,5]. Codon usage analysis has been applied to prokaryote and eukaryote, such as Escherichia coli, Bacillus subtilis, Saccharomyces cerevisiae, Caenorhabditis elegans and human beings [6-8]. These observed patterns in synonymous codon usage varied among genes within a genome, and among genomes. The codon usage is attributable to the equilibrium between natural selection and mutation pressure [9,10]. Recent studies of viral codon usage has shown that mutation bias may be a more important factor than natural selection in determining codon usage bias of some viruses, such as Picornaviridae, Pestivirus, plant viruses, and vertebrate DNA viruses [9,11-13]. Meanwhile, recent report also showed that the G+C compositional constraint is the main factor that determines the codon usage bias in iridovirus genomes[11,14]. Analysis of codon usage can reveal much about the molecular evolution or individual genes of the viruses. Polioviruses belong to the family Picornaviridae and are classified as human enterovirus C (HEV-C) species in the genus Enterovirus according to the current taxonomy [15,16]. Polioviruses can be divided into three different genotypes: 1, 2 and 3. The genome of each genotypes contains a single positive-stranded RNA with a size of approximately 6 kb consisting of a single large open reading frame (ORF) flanked by 5 and 3 untranslated region [17]. As we known, the Sabin oral poliovaccine (OPV) was among the best known viral vaccines [18]. It has saved the lives and health of innumerable people, in particular children. However, poliovirus is highly genetically variable. OPV viruses may undergo transformation into circulating highly diverged VDPV, exhibiting properties hardly distinguishable from those of wild polioviruses [19]. So far, little information about synonymous codon usage pattern of polioviruses genome has been acquired to date. To our knowledge, this is the first report of the codon usage analysis on polioviruses (including wild strains, attenuated live vaccine strains and VDPV strains). In this study, we analyzed the codon usage data and base composition of 48 available representative complete ORFs of poliovirus to obtain some clues to the features of genetic evolution of the virus. Methods Sequence data A total of 48 poliovirus genomes were used in this study (Table 1). The serial number (SN), genotype, length value, isolated region, GenBank accession numbers, and (...truncated)


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Jie Zhang, Meng Wang, Wen-qian Liu, Jian-hua Zhou, Hao-tai Chen, Li-na Ma, Yao-zhong Ding, Yuan-xing Gu, Yong-sheng Liu. Analysis of codon usage and nucleotide composition bias in polioviruses, Virology Journal, 2011, pp. 146, 8, DOI: 10.1186/1743-422X-8-146