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. 2020 Sep 27;21(19):7129.
doi: 10.3390/ijms21197129.

Analysis of the Codon Usage Pattern of HA and NA Genes of H7N9 Influenza A Virus

Jiumeng Sun  1 , Wen Zhao  1 , Ruyi Wang  1 , Wenyan Zhang  1 , Gairu Li  1 , Meng Lu  1 , Yuekun Shao  1 , Yichen Yang  1 , Ningning Wang  1 , Qi Gao  1 , Shuo Su  1
Affiliations

Analysis of the Codon Usage Pattern of HA and NA Genes of H7N9 Influenza A Virus

Jiumeng Sun et al. Int J Mol Sci. .

Abstract

Novel H7N9 influenza virus transmitted from birds to human and, since March 2013, it has caused five epidemic waves in China. Although the evolution of H7N9 viruses has been investigated, the evolutionary changes associated with codon usage are still unclear. Herein, the codon usage pattern of two surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA), was studied to understand the evolutionary changes in relation to host, epidemic wave, and pathogenicity. Both genes displayed a low codon usage bias, with HA higher than NA. The codon usage was driven by mutation pressure and natural selection, although the main contributing factor was natural selection. Additionally, the codon adaptation index (CAI) and deoptimization (RCDI) illustrated the strong adaptability of H7N9 to Gallus gallus. Similarity index (SiD) analysis showed that Homo sapiens posed a stronger selection pressure than Gallus gallus. Thus, we assume that this may be related to the gradual adaptability of the virus to human. In addition, the host strong selection pressure was validated based on CpG dinucleotide content. In conclusion, this study analyzed the usage of codons of two genes of H7N9 and expanded our understanding of H7N9 host specificity. This aids into the development of control measures against H7N9 influenza virus.

Keywords: H7N9; HA gene; NA gene; codon usage bias; host specificity.

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Conflict of interest statement

The author states that the research is in the absence of any competitive interests and conflicts.

Figures

Figure 1
Figure 1
Maximum likelihood (ML) trees of H7N9 hemagglutinin (HA) (A) and neuraminidase (NA) (B) genes were reconstructed using RAxML (v8.2.10) with 1000 replications. The environment, human, and avian are represented in orange, beige, and cyan, respectively. Dark purple, olive green, light yellow, orange, and light purple correspond to waves 1 to 5. Grass green corresponds to high pathogenicity. HP: high pathogenicity.
Figure 2
Figure 2
PCA taxonomic analysis of HA (left column) and NA (right column). The environment, human, and avian are represented in orange, beige, and cyan, respectively. Circles are marked by dark purple, olive green, light yellow, orange, and light purple, corresponding to waves 1 to 5, respectively. Grass green corresponds to high pathogenicity.
Figure 3
Figure 3
Effective number of codon (ENC) analysis of HA (displayed in pink and black dot histogram) and NA (displayed in earthy yellow and gray squares histogram) of different waves (A), hosts (B), and pathogenicity (C). The cut-off value of the ENC value is 35. The larger the ENC value, the lower the codon usage bias.
Figure 4
Figure 4
Left column and right column of ENC-plot analysis represent the HA and NA genes, respectively. The environment, human, and avian are represented in orange, beige, and cyan, respectively. Dark purple, olive green, light yellow, orange, and light purple correspond to waves 1 to 5, respectively. Grass green corresponds to high pathogenicity.
Figure 5
Figure 5
Parity Rule 2 (PR2) analysis of HA and NA of different classification. Far away from the origin indicates that there is a bias between the effect of mutation pressure and natural selection.
Figure 6
Figure 6
Neutrality analysis of HA and NA depicted by plotting GC3s against GC12s. The higher the slope, the greater the effect of natural selection pressure. The environment, human, and avian are represented in orange, beige, and cyan, respectively. Dark purple, olive green, light yellow, orange, and light purple correspond to waves 1 to 5, respectively. Grass green corresponds to high pathogenicity.
Figure 7
Figure 7
Codon adaptation index (CAI) and relative codon deoptimization index (RCDI) analysis of HA and NA. The coordinate axis was divided into two segments, and then placed the above two analyses on the same figure for observation. CAI corresponds to dark purple for avian and coffee for human. In RCDI, dark red and dark green represent Gallus gallus and Homo sapiens, respectively. Cylindrical maps are classified according to different taxonomy with SiD values as ordinates. Blue and yellow are used to represent Homo sapiens and Gallus gallus, respectively.
Figure 8
Figure 8
The ratio of CpG dinucleotide of strains of avian and human in HA and NA. When the relative dinucleotide abundances are <0.78, it indicates that dinucleotides are underrepresented. The color distribution is consistent with the previous figure.
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