Department of Epidemiology, Ministry of Education Key Laboratory of Public Health Safety (Fudan University), School of Public Health, Fudan University, Shanghai, 200032, China.
Institute of Communicable Diseases Prevention and Control, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, 310052, Zhejiang, China.
BMC Genomics. 2022 Jul 16;23(1):518. doi: 10.1186/s12864-022-08730-2.
Group A rotavirus (RVA) is a common causative agent of acute gastroenteritis in infants and young children worldwide. RVA P genotypes, determined by VP4 sequences, have been confirmed to infect humans and animals. However, their codon usage patterns that are essential to obtain insights into the viral evolution, host adaptability, and genetic characterization remained unclear, especially across animal hosts.
We performed a comprehensive codon usage analysis of eight host-specific RVA P genotypes, including human RVA (P[4] and P[8]), porcine RVA (P[13] and P[23]), and zoonotic RVA (P[1], P[6], P[7] and P[19]), based on 233 VP4 complete coding sequences. Nucleotide composition, relative synonymous codon usage (RSCU), and effective number of codons (ENC) were calculated. Principal component analysis (PCA) based on RSCU values was used to explore the codon usage patterns of different RVA P genotypes. In addition, mutation pressure and natural selection were identified by using ENC-plot, parity rule 2 plot, and neutrality plot analyses. All VP4 sequences preferred using A/U nucleotides (A: 0.354-0.377, U: 0.267-0.314) than G/C nucleotides across genotypes. Similarly, majority of commonly used synonymous codons were likely to end with A/U nucleotides (A: 9/18-12/18, U: 6/18-9/18). In PCA, human, porcine, and zoonotic genotypes clustered separately in terms of RSCU values, indicating the host-specific codon usage patterns; however, porcine and zoonotic genotypes were partly overlapped. Human genotypes, P[4] and P[8], had stronger codon usage bias, as indicated by more over-represented codons and lower ENC, compared to porcine and zoonotic genotypes. Moreover, natural selection was determined to be a predominant driver in shaping the codon usage bias across the eight P genotypes. In addition, mutation pressure contributed to the codon usage bias of human genotypes.
Our study identified a strong codon usage bias of human RVA P genotypes attributable to both natural selection and mutation pressure, whereas similar codon usage bias between porcine and zoonotic genotypes predominantly attributable to natural selection. It further suggests possible cross-species transmission. Therefore, it warrants further surveillance of RVA P genotypes for early identification of zoonotic infection.
A 组轮状病毒（RVA）是全球婴幼儿急性肠胃炎的常见致病原。通过 VP4 序列确定的 RVA P 基因型已被证实可感染人类和动物。然而，它们的密码子使用模式对于深入了解病毒进化、宿主适应性和遗传特征至关重要，尤其是在动物宿主中。
我们对 8 种宿主特异性 RVA P 基因型（包括人源 RVA [P[4]和 P[8]]、猪源 RVA [P[13]和 P[23]]和人畜共患 RVA [P[1]、P[6]、P[7]和 P[19]]）进行了全面的密码子使用分析，共基于 233 个 VP4 完整编码序列。计算核苷酸组成、相对同义密码子使用（RSCU）和有效密码子数（ENC）。基于 RSCU 值的主成分分析（PCA）用于探索不同 RVA P 基因型的密码子使用模式。此外，通过 ENC-plot、奇偶校验规则 2 plot 和中性 plot 分析鉴定突变压力和自然选择。所有 VP4 序列都偏爱使用 A/U 核苷酸（A：0.354-0.377，U：0.267-0.314）而不是 G/C 核苷酸。同样，大多数常用的同义密码子很可能以 A/U 核苷酸结尾（A：9/18-12/18，U：6/18-9/18）。在 PCA 中，根据 RSCU 值，人源、猪源和人畜共患基因型聚类分开，表明存在宿主特异性密码子使用模式；然而，猪源和人畜共患基因型部分重叠。与猪源和人畜共患基因型相比，人源基因型 P[4]和 P[8]具有更强的密码子使用偏好，表现为更多过度表达的密码子和更低的 ENC。此外，自然选择被确定为塑造 8 种 P 基因型密码子使用偏好的主要驱动力。此外，突变压力导致人源基因型的密码子使用偏好。
我们的研究确定了人源 RVA P 基因型的强烈密码子使用偏好归因于自然选择和突变压力，而猪源和人畜共患基因型之间的类似密码子使用偏好主要归因于自然选择。这进一步表明可能存在跨物种传播。因此，有必要对 RVA P 基因型进行进一步监测，以早期发现人畜共患感染。
