通过古老和现代基因组追踪CCR5delta32删除的进化历史
Kirstine Ravn1, Leonardo Cobuccio1, Rasa Audange Muktupavela2
1Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Cell
|May 6, 2025
概括
与艾滋病毒耐药性相关的CCR5-delta32变种起源于西欧亚,早在6700年前. 这种遗传删除经历了积极选择,影响了其传播和治疗向.
科学领域:
- 人口遗传学
- 人类的进化
- 基因组学
背景情况:
- 这种CCR5-delta32基因与HIV-1耐药性有关,并且具有有争议的进化历史,特别是其在欧洲人群中的频率.
- 了解CCR5-delta32等遗传变异的起源和传播对于进化研究和治疗开发至关重要.
研究的目的:
- 阐明CCR5-delta32删除的进化历史和时空起源.
- 研究对CCR5-delta32单元型的选择性压力.
- 解释CCR5-delta32在拉丁美洲的存在及其对基于CCR5受体的疗法的影响.
主要方法:
- 开发了一个利用84个预先存在的变体的类型感知概率模型.
- 选了934个低覆盖率的古老基因组来追踪CCR5-delta32删除的起源.
- 分析了古老的DNA数据以确定对CCR5-delta32单元型的积极选择.
主要成果:
- CCR5-delta32删除至少起源于公元前6700年在西欧亚大草原的一个特定的单元型.
- 在公元前8000年至2000年间,在西欧亚洲发现了CCR5-delta32单元型的强有力的证据.
- 拉丁美洲CCR5-delta32的存在归因于哥伦布后的遗传混合.
结论:
- 这项研究为CCR5-delta32删除提供了详细的进化时间表,追溯到古代西欧亚.
- 积极选择显著影响了CCR5-delta32单元型的分布.
- 针对CCR5的治疗策略需要仔细考虑复杂的基因型-型-表型关系.
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