在分泌的粘真菌,MUC5AC和MUC5B中的结构和遗传多样性
Elizabeth G Plender1,2, Timofey Prodanov3,4, PingHsun Hsieh1
1Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
bioRxiv : the preprint server for biology
|April 2, 2024
概括
分泌的粘膜MUC5AC和MUC5B对呼吸道防御至关重要. 这项研究使用长读测序来揭示MUC5AC和MUC5B的结构多样性,揭示了人类MUC5AC的进化变化和种群特定的选择压力.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 进化生物学 进化生物学
背景情况:
- 分泌的粘膜MUC5AC和MUC5B对于呼吸道防御至关重要,捕获病原体并帮助粘膜清除.
- 它们的结构以可变数串联重复 (VNTR) 为特征,对短读测序和分析提出了挑战.
研究的目的:
- 描述人类和非人类灵长类动物 (NHP) MUC5AC和MUC5B基因的结构多样性.
- 为了研究进化模式和对MUC5AC.起作用的种群特异性选择.
主要方法:
- 长读测序和组装206个人类和20个NHP单元型.
- 对VNTR拷贝数变异,蛋白质长度,链接不平衡 (LD) 和塔吉马的D.的分析.
- 来自1000个基因组项目的2600个人的MUC5AC单元组的基因定型.
主要成果:
- 人类MUC5B在很大程度上是不变的,观察到一些扩展的VNTR单元型.
- MUC5AC表现出显著的等位基变异,其中30种变异编码16种不同的蛋白质,分为三个分类 (H1,H2,H3).
- 人类MUC5AC变种通常比NHP对应物更短,这表明进化减少. 东亚人在H1/H2中显示出大量的MUC5AC LD块和选择特征,而非洲人和欧洲人在H3中显示出平衡选择.
结论:
- 长读测序提供了一个强大的策略,用于表征素基因中复杂的VNTR区域.
- 进化压力塑造了MUC5AC的多样性,在人类种群中观察到不同的选择模式.
- 了解MUC5AC结构变异可以改善疾病关联研究.
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