2022年人类猴痘(hMPX)的出现和持续爆发是一个严重的全球威胁。在单基因水平上了解猴痘病毒(MPXV)的进化可能会为探索当前爆发的独特方面提供线索:迅速扩大和持续的人与人之间的传播。对于目前的调查,156个MPXV编码基因的等位基因(占基因组序列的>95%)已从大约1,500个分离株中收集,包括那些对以前的疫情负责的人。使用一系列分子进化方法,我们证明了种内同源重组对MPXV进化的影响可以忽略不计。尽管大多数MPXV基因(64.10%)在整个基因水平上都进行了阴性选择,发现10个MPXV编码基因(MPXVgp004、010、012、014、044、098、138、178、188和191)具有已知在正向达尔文选择下进化的总共15个密码子或氨基酸位点。除MPXVgp138外,几乎所有这些基因都编码与宿主相互作用的蛋白质。其中,五种锚蛋白(MPXVgp004、010、012、178和188)和一种Bcl-2样蛋白(MPXVgp014)参与痘病毒宿主范围的测定。我们发现大多数(80%)阳性氨基酸取代出现在几十年前,表明这些位点一直处于恒定的选择压力下,并且适应性更强的等位基因已在天然储层中循环。基因等位基因的最小跨越网络也支持了这一发现。三个阳性氨基酸取代(MPXVgp010中的T/A426V,MPXVgp012中的A423D和MPXVgp191中的S105L)出现在2019年或2022年,表明它们对于病毒最终适应人类至关重要。蛋白质建模表明,正氨基酸取代可能以多种方式影响蛋白质功能。进一步的研究应集中在揭示基因中氨基酸取代阳性对病毒适应人类的生物学效应。毒力,传输,等等。我们的研究提高了MPXV适应机制的知识,并为探索导致当前爆发的独特方面的因素提供了见解。
The emerging and ongoing outbreak of human monkeypox (hMPX) in 2022 is a serious global threat. An understanding of the evolution of the monkeypox virus (MPXV) at the single-gene level may provide clues for exploring the unique aspects of the current outbreak: rapidly expanding and sustained human-to-human transmission. For the current investigation, alleles of 156 MPXV coding genes (which account for >95% of the genomic sequence) have been gathered from roughly 1,500 isolates, including those responsible for the previous outbreaks. Using a range of molecular evolution approaches, we demonstrated that intra-species homologous recombination has a negligible effect on MPXV evolution. Despite the fact that the majority of the MPXV genes (64.10%) were subjected to negative selection at the whole gene level, 10 MPXV coding genes (MPXVgp004, 010, 012, 014, 044, 098, 138, 178, 188, and 191) were found to have a total of 15 codons or amino acid sites that are known to evolve under positive Darwinian selection. Except for MPXVgp138, almost all of these genes encode proteins that interact with the host. Of these, five
ankyrin proteins (MPXVgp004, 010, 012, 178, and 188) and one Bcl-2-like protein (MPXVgp014) are involved in poxviruses\' host range determination. We discovered that the majority (80%) of positive amino acid substitutions emerged several decades ago, indicating that these sites have been under constant selection pressure and that more adaptable alleles have been circulating in the natural reservoir. This finding was also supported by the minimum spanning networks of the gene alleles. The three positive amino acid substitutions (T/A426V in MPXVgp010, A423D in MPXVgp012, and S105L in MPXVgp191) appeared in 2019 or 2022, indicating that they would be crucial for the virus\' eventual adaptation to humans. Protein modeling suggests that positive amino acid substitutions may affect protein functions in a variety of ways. Further study should focus on revealing the biological effects of positive amino acid substitutions in the genes for viral adaptation to humans, virulence, transmission, and so on. Our study advances knowledge of MPXV\'s adaptive mechanism and provides insights for exploring factors that are responsible for the unique aspects of the current outbreak.