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. 2017 Aug 23;18(1):652.
doi: 10.1186/s12864-017-4063-1.

Genetic and codon usage bias analyses of polymerase genes of equine influenza virus and its relation to evolution

Bidhan Ch Bera  1 , Nitin Virmani  2 , Naveen Kumar  3 , Taruna Anand  1 , S Pavulraj  1 , Adam Rash  4 , Debra Elton  4 , Nicola Rash  4 , Sandeep Bhatia  3 , Richa Sood  3 , Raj Kumar Singh  5 , Bhupendra Nath Tripathi  1
Affiliations

Genetic and codon usage bias analyses of polymerase genes of equine influenza virus and its relation to evolution

Bidhan Ch Bera et al. BMC Genomics. .

Abstract

Background: Equine influenza is a major health problem of equines worldwide. The polymerase genes of influenza virus have key roles in virus replication, transcription, transmission between hosts and pathogenesis. Hence, the comprehensive genetic and codon usage bias of polymerase genes of equine influenza virus (EIV) were analyzed to elucidate the genetic and evolutionary relationships in a novel perspective.

Results: The group - specific consensus amino acid substitutions were identified in all polymerase genes of EIVs that led to divergence of EIVs into various clades. The consistent amino acid changes were also detected in the Florida clade 2 EIVs circulating in Europe and Asia since 2007. To study the codon usage patterns, a total of 281,324 codons of polymerase genes of EIV H3N8 isolates from 1963 to 2015 were systemically analyzed. The polymerase genes of EIVs exhibit a weak codon usage bias. The ENc-GC3s and Neutrality plots indicated that natural selection is the major influencing factor of codon usage bias, and that the impact of mutation pressure is comparatively minor. The methods for estimating host imposed translation pressure suggested that the polymerase acidic (PA) gene seems to be under less translational pressure compared to polymerase basic 1 (PB1) and polymerase basic 2 (PB2) genes. The multivariate statistical analysis of polymerase genes divided EIVs into four evolutionary diverged clusters - Pre-divergent, Eurasian, Florida sub-lineage 1 and 2.

Conclusions: Various lineage specific amino acid substitutions observed in all polymerase genes of EIVs and especially, clade 2 EIVs underwent major variations which led to the emergence of a phylogenetically distinct group of EIVs originating from Richmond/1/07. The codon usage bias was low in all the polymerase genes of EIVs that was influenced by the multiple factors such as the nucleotide compositions, mutation pressure, aromaticity and hydropathicity. However, natural selection was the major influencing factor in defining the codon usage patterns and evolution of polymerase genes of EIVs.

Keywords: Codon usage bias; Equine influenza virus; Evolution; H3N8; Polymerase genes.

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Figures

Fig. 1
Fig. 1
Phylogenetic analyses of polymerase genes of EIVs. The trees were generated by the maximum likelihood model implemented in the software MEGA 5.0. The reliability of the trees was assessed by bootstrap with 1000 replications. The bootstrap values higher than 0.7 are highlighted with solid black dots. The distinct Florida clade 1 and clade 2 sublineages of EIVs have been represented by colored boxes
Fig. 2
Fig. 2
Comparison of phylogenetic derived clusters of EIVs polymerase genes based on their effective number of codon (ENc) values
Fig. 3
Fig. 3
Magnitude of significant determining factors of codon usage bias in polymerase genes of EIVs. ENc-plot: the red dotted line represents the expected curve of positions of strains when the codon usage was only determined by the GC3s composition. Neutrality plot: the red dotted line is the linear regression of GC12 against GC3. PR2 bias plot: AU-bias [A3/(A3 + U3)] at the third codon position of the four-codon amino acids of entire genes were plotted against the GC-bias [G3/(G3 + C3)] and the centre of the plot represents no bias between the influence of the mutation pressure and natural selection
Fig. 4
Fig. 4
Correspondence analysis (COA) of the synonymous codon usage in EIVs polymerase genes. a COA generated axes contributions. The relative and cumulative inertia of the first 20 factors from a COA of the synonymous codon usage frequencies, (b) COA of the synonymous codon usage towards codons. This analysis was built on the RSCU values of the 59 synonymous codons. The positions of each codon were plotted on the first two-main-dimensional coordinates. Different base ended codons were color labelled. c COA of the synonymous codon usage in coding sequences of polymerase genes of EIV isolates. The positions of each polymerase genes of EIV isolates were plotted on the first two-main-axes
Fig. 5
Fig. 5
The RCDI analysis of phylogenetic derived clusters of EIVs polymerase genes in relation to their host species, Equus caballus
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