背景:A组轮状病毒(RVA)是全球婴幼儿急性胃肠炎的常见病原体。RVAP基因型,由VP4序列确定,已被证实感染人类和动物。然而,它们的密码子使用模式对于了解病毒进化至关重要,宿主适应性,遗传特征仍不清楚,尤其是动物宿主。
结果:我们对八种宿主特异性RVAP基因型进行了全面的密码子使用分析,包括人类RVA(P[4]和P[8]),猪RVA(P[13]和P[23]),和人畜共患RVA(P[1],P[6],P[7]和P[19]),基于233个VP4完整编码序列。核苷酸组成,相对同义密码子使用(RSCU),计算有效密码子数(ENC)。基于RSCU值的主成分分析(PCA)用于探索不同RVAP基因型的密码子使用模式。此外,通过使用ENC-plot鉴定突变压力和自然选择,奇偶校验规则2图,和中立情节分析。所有VP4序列优选使用A/U核苷酸(A:0.354-0.377,U:0.267-0.314)而不是跨基因型的G/C核苷酸。同样,大多数常用的同义密码子可能以A/U核苷酸结束(A:9/18-12/18,U:6/18-9/18)。在PCA中,人类,猪,和人畜共患基因型在RSCU值方面分别聚集,表明宿主特定的密码子使用模式;然而,猪和人畜共患基因型部分重叠。人类基因型,P[4]和P[8],有更强的密码子使用偏好,如更多的过度代表密码子和更低的ENC所示,与猪和人畜共患基因型相比。此外,自然选择被确定为影响8种P基因型密码子使用偏倚的主要驱动因素.此外,突变压力导致人类基因型的密码子使用偏差。
结论:我们的研究发现,由于自然选择和突变压力,人类RVAP基因型存在强烈的密码子使用偏好,而猪和人畜共患基因型之间相似的密码子使用偏差主要归因于自然选择。它进一步表明可能的跨物种传播。因此,需要进一步监测RVAP基因型,以便早期识别人畜共患感染.
BACKGROUND: 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.
RESULTS: 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.
CONCLUSIONS: 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.