Genome-wide analysis of the synonymous codon usage pattern of Streptococcus suis

Abstract

Streptococcus suis (S. suis) is a gram-positive coccus that causes disease in humans and animals. The codon usage pattern of bacteria reveals a range of evolutionary changes that assist them to enhance tolerance to environments. To better understand the genetic features during the evolution of S. suis, we performed codon usage analysis. Nine pathogenic strains of different serotypes and different geographical distribution were analyzed to better understand the differences in their evolutionary process. Nucleotide compositions and relative synonymous codon usage (RSCU) analysis revealed that A/T-ending codons are dominant in S. suis. Neutrality analysis, correspondence analysis and ENC-plot results revealed that natural selection is the predominant element prompting codon usage. Cluster analysis based on RSCU was roughly consistent with the dendrogram rooted genomic BLAST analysis. Comparison of synonymous codon usage pattern between S. suis and susceptible hosts (H. sapiens and S. scrofa) revealed that the codon usage of S. suis is separated from the synonymous codon usage of susceptible hosts. The CAI values implied that S. suis includes a series of predicted highly expressed coding sequences contained in metabolism and transcriptional regulation, revealing the necessity of this pathogen to deal with various environmental conditions. The study of codon usage in S. suis may provide evidence involving the molecular evolution of bacteria and a better understanding of evolutionary relationships between S. suis and its corresponding hosts.

Introduction

Streptococcus suis (S. suis) is an emerging zoonotic pathogen, not only causing meningitis in pigs and humans with high mortality and morbidity, but also responsible for various diseases such as septicemia with sudden death, endocarditis, and arthritis [[1], [2], [3]]. Based on the capsular antigens of its capsular polysaccharides, S. suis can be classified into 33 serotypes [4]. The number of human infections with S. suis has increased over the past few years worldwide, particularly in Southeast Asia [5]. In addition, it has also been reported that S. suis can colonize the upper respiratory and gastrointestinal tracts of various animals (ruminants, cats, dogs and horses) [6]. When colonized in the respiratory tract of host, S. suis usually induce chronic or persistent infections [7], thus, S. suis seriously impacts the pig industry and human health.

Although the genetic code is redundant, synonymous codons are not used equally, which is called codon usage bias [8]. Codon usage bias (CUB) generally exists in all kinds of organisms such as viruses [[9], [10], [11], [12]], bacteria [[13], [14], [15], [16], [17], [18]], fungi [19], plants [20,21] and animals [22]. The genomes of free-living unicellular organisms such as bacteria have strong codon usage bias with different degrees of bias among genes [23]. The balance between mutation pressure and natural selection lead to translational efficiency of genes [24]. Many factors may affect the codon usage of bacteria, such as mutation pressure [25], gene length [26], natural selection [27], amount and type of available tRNAs [28] and amino acid composition [18]. CUB at the genome level can explain the molecular evolution of a single gene and help to reveal the evolutionary process of an organism [17]. CUB can also help heterologous protein expressed in certain species and molecular genetic engineering to optimize codon [31]. In addition, it aids in revealing the relationship between the host and pathogenic microorganism [32].

Until now it is indistinct whether there are variations in gene expression based upon selection pressure. Hence, we analyzed the codon usage bias of S. suis genes comprehensively, using correlation analysis and multivariate statistical techniques. In order to obtain insight into the genetic evolution of S. suis, we explored the relationship between the codon usage bias of S. suis and host adaptation to better understand the evolution of S. suis.