Genome-Wide Analysis of Codon Usage and Influencing Factors in Chikungunya Viruses

Azeem Mehmood Butt,Izza Nasrullah,Yigang Tong,Fausto Baldanti

doi:10.1371/journal.pone.0090905

Abstract

Chikungunya virus (CHIKV) is an arthropod-borne virus of the family Togaviridae that is transmitted to humans by Aedes spp. mosquitoes. Its genome comprises a 12 kb single-strand positive-sense RNA. In the present study, we report the patterns of synonymous codon usage in 141 CHIKV genomes by calculating several codon usage indices and applying multivariate statistical methods. Relative synonymous codon usage (RSCU) analysis showed that the preferred synonymous codons were G/C and A-ended. A comparative analysis of RSCU between CHIKV and its hosts showed that codon usage patterns of CHIKV are a mixture of coincidence and antagonism. Similarity index analysis showed that the overall codon usage patterns of CHIKV have been strongly influenced by Pan troglodytes and Aedes albopictus during evolution. The overall codon usage bias was low in CHIKV genomes, as inferred from the analysis of effective number of codons (ENC) and codon adaptation index (CAI). Our data suggested that although mutation pressure dominates codon usage in CHIKV, patterns of codon usage in CHIKV are also under the influence of natural selection from its hosts and geography. To the best of our knowledge, this is first report describing codon usage analysis in CHIKV genomes. The findings from this study are expected to increase our understanding of factors involved in viral evolution, and fitness towards hosts and the environment.

Highlights

Chikungunya virus (CHIKV), a member of the genus alphavirus of the family Togaviridae, is a small (60–70 nm), enveloped, singlestrand positive-sense RNA virus
A clearer picture of overall nucleotide composition that could influence the codon usage preference in CHIKV genomes emerged from the analysis of the nucleotide composition of the third position of codons (A3, U3, G3, C3) and of GC1, GC1,2, GC3 and AU3 (Table 1)
In the case of ARO, an opposite trend was observed: ARO values were significantly negatively correlated with f91 and correlations with f92, effective number of codons (ENC), GC3 and GC were not significant (Table 6). These results indicated that, natural selection has influenced codon usage of CHIKV genomes to some extent, it is much weaker compared with mutational pressure

Summary

Introduction

Chikungunya virus (CHIKV), a member of the genus alphavirus of the family Togaviridae, is a small (60–70 nm), enveloped, singlestrand positive-sense RNA virus. The CHIKV genome is arranged in the order of 5-9cap-nsP1nsP2-nsP3-nsP4-(junction region)-C-E3-E2-6K-E1-poly(A)-39 [1]. CHIKV infection is characterized by abrupt onset of high fever, headache, rashes, arthralgia and myalgia. The typical clinical sign of the disease is poly-arthralgia, which is a very painful condition affecting joints and may persist for several months to years in some cases [7]. It is generally accepted that CHIKV originated from Africa, where it is primarily maintained in a yellow fever-like zoonotic sylvatic cycle and depends upon non-human primates and arboreal, peridomestic mosquitoes as reservoir hosts. The spread of CHIKV in Asia and urban endemics are associated with a dengue-like ‘‘human-mosquito-human’’ direct transmission cycle, where A. aegypti and A. albopuctus serve as primary transmission vectors and humans serve as hosts [7,8,9]

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Conclusion