古代ACE2中积极选择的向性表明了蝙蝠特异性适应宿主冠状病毒的替代假设
Yuan-Ting Guo1,2, Ji-Bin Jiang2,3, Guan-Rong Qiao4
1College of Life Sciences, Northwest University, Xi'an 710127, China.
概括
蝙蝠进化了增强的 ангиотензин转化酶2 (ACE2) 通过积极选择. 这种古老的ACE2变种显示出更强的活性,提高了运动表现,并减少了SARS-CoV-2结合,为蝙蝠病毒抵抗提供了洞察力.
科学领域:
- 进化生物学是进化的生物学.
- 哺乳动物遗传学 哺乳动物遗传学
- 病毒学 病毒学
背景情况:
- ангиотензин转化酶2 (ACE2) 在心血管功能中起着关键作用,并作为病毒进入受体.
- 蝙蝠作为病毒的天然储存体,表现出与ACE2进化潜在相关的独特适应性.
- 之前的观察表明,蝙蝠具有与其生理和病毒受体功能相关的改变ACE2特征.
研究的目的:
- 为了研究祖先蝙蝠血统中ACE2上的进化变化和选择压力.
- 功能性地描述祖先蝙蝠ACE2 (AncBat-ACE2) 并评估积极选择的影响.
- 探索AncBat-ACE2与心血管生理学和冠状病毒相互作用有关的双重功能.
主要方法:
- 在祖先蝙蝠分支沿线对ACE2的选择压力的分析.
- 恢复AncBat-ACE2和一个突变版本 (AncBat-ACE2-mut) 与改变的网站.
- 生物化学测试用于比较酶活性和病毒结合亲和力.
- 在小鼠身上进行生理评估,以评估运动疲劳表现.
主要成果:
- 在AncBat-ACE2.2.中检测到一个显著的积极选择特征.
- 与其突变形式相比,复活的AncBat-ACE2显示出增强的酶活性.
- AncBat-ACE2改善了小鼠的运动表现,并表现出对SARS-CoV-2的结合亲和力减少.
- 这些发现突出了功能性变性,即单个遗传变化影响多个特征.
结论:
- 阳性选择塑造了蝙蝠ACE2,赋予了增强的生理功能和改变的病毒相互作用.
- 古老的蝙蝠ACE2变体可能代表一种进化适应,用于管理与飞行相关的需求和病毒防御.
- 这项研究提出了一种新的假设,即通过ACE2适应,蝙蝠对冠状病毒的耐药性的进化起源.
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