隐藏的进化约束决定了冠状病毒辅助基因的保留
Stephen A Goldstein1,2, Teagan M Feeley1, Kristina M Babler1
1Department of Human Genetics, University of Utah School of Medicine, Salt Lake City UT 84112, USA.
bioRxiv : the preprint server for biology
|October 24, 2023
概括
冠状病毒中的辅助基因令人惊地稳定. 小鼠肝炎病毒 (MHV) 的实验进化表明,即使是非功能性基因也可以保留,这对病毒基因组进化提出了挑战.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 进化生物学 进化生物学
背景情况:
- 冠状病毒通过辅助基因获取进行基因创新.
- 辅助基因会影响病毒宿主范围和热带性,但它们的进化动态尚不清楚.
- 病毒基因组的可变区域的选择压力在很大程度上仍然没有特征.
研究的目的:
- 通过实验进化,模拟冠状病毒中辅助基因的进化命运.
- 研究作用于病毒辅助基因的选择性压力,包括来自细胞基因或基因重复的基因.
- 为了比较小鼠肝炎病毒 (MHV) 和SARS-CoV-2中的辅助基因的进化模式.
主要方法:
- 在连续感染下,小鼠肝炎病毒 (MHV) 的实验演变.
- 在MHV基因组中包含细胞AKAP7固酶和非活性本源固酶 (NS2).
- 分析病毒复制,亚基因组RNA比例和斑块净化隔离物中的基因完整性.
- 对SARS-CoV-2 ORF8基因进化与MHV ORF2.2相关的比较分析.
主要成果:
- 编码非活跃NS2 (ORF2) 的基因在连续感染下保持完整,表明了神秘的约束.
- AKAP7在强有力的选择下保留了,但在放松的选择下失去了.
- 实验进化改变了MHV细胞类型特异复制和亚基因组RNA配置文件,揭示了适应机制.
- 编码缺陷的SARS-CoV-2 ORF8基因在很大程度上保持完整,类似于MHV ORF2模式.
结论:
- 由于神秘的约束,非功能性病毒辅助基因可以被保留,这挑战了基因损失的典型模型.
- 病毒辅助基因表现出复杂的进化动态,受选择和功能约束的影响.
- 来自MHV实验进化的发现为SARS-CoV-2 ORF8和其他β冠状病毒的进化轨迹提供了洞察力.
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