Comprehensive analysis of synonymous codon usage patterns and influencing factors of porcine epidemic diarrhea virus

Abstract

Porcine epidemic diarrhea virus (PEDV) is an enteric pathogen belonging to the family Coronaviridae that causes the porcine epidemic diarrhea, a highly contagious disease with high mortality in piglets and symptoms that include dehydration and severe diarrhea. Considering the high frequency of genetic mutations in PEDV and its potential for interspecies transmission, as it can infect and replicate in bat and human cells, a comprehensive analysis of its codon usage bias was performed. The effective number of codons (ENC) and the relative synonymous codon usage (RSCU) were determined, revealing codon usage bias in the PEDV genome. Principal component analysis (PCA), an ENC plot, and a parity rule 2 (PR2) plot showed that mutation pressure and natural selection have influenced the codon usage bias of the PEDV genomes. Correlation analysis with GRAVY and aromaticity values and neutrality plot analysis indicated that natural selection was the main force influencing the codon usage pattern, while mutation pressure played a minor role. This study provides valuable basic data for further fundamental research on evolution of PEDV.

Fig. 1

ENC plots showing the relationship between ENC values and GC3s values. Each point represents one PEDV strain. (A) points classified by country. (B) points classified by continent. All of the points were below the standard curve, indicating that mutational pressure and other factors both play a role in PEDV codon usage.

Fig. 2

Principal component analysis of PEDV. Each point represents one PEDV strain. (A) The distributions of the first 20 vectors by PCA. Columns represent the relative inertia, and the curve represents the cumulative inertia. (B) PCA plot constructed with the first two axes according to country. (C) PCA plot according to continent. (D) PCA plot according to date

Fig. 3

PR2 plot analysis. The PR2 bias plot was calculated for the complete PEDV genome.

Fig. 4

Neutrality analysis performed by plotting GC12s values against GC3s values for the complete genome. The regression line is represented by the black straight line. The regression equation is also shown.

Fig. 5

Neutrality analysis performed for each gene. (A) ORF1ab, (B) S, (C) ORF3, (D) E, (E) M, (F) N