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祖先序列重建的稳定性,以在地点和谱系之间演化异质性
Ricardo Muñiz-Trejo1, Yeonwoo Park2,3, Joseph W Thornton1,4
1Department of Ecology and Evolution, University of Chicago, Chicago, IL, USA.
Molecular biology and evolution
|April 9, 2025
概括
祖先序列重建对进化异质性是强大的. 提高准确性依赖于密集采样的对齐以最大限度地提高遗传学信号,而不是复杂的模型.
科学领域:
- 进化生物学是进化的生物学.
- 生物信息学是一种生物信息学.
- 计算生物学是一种计算生物学.
背景情况:
- 祖先序列重建 (ASR) 通常使用同质的进化模型,假设在各个地点和谱系中均的替代率.
- 现实生物系统由于不同的结构/功能约束和表观症而表现出异质性,违反了这些假设.
研究的目的:
- 在现实的进化条件下,评估违反同质性假设对ASR准确性的影响.
- 评估来自ASR深度突变扫描数据的特定站点替代模型的性能.
主要方法:
- 开发了特定站点的替代模型,通过三种蛋白质家族的深度突变扫描数据进行参数化.
- 在实证和模拟对齐上使用异质和均质模型进行祖先序列重建.
- 分析了模型选择和数据异质性对重建的祖先序列的影响.
主要成果:
- 在经验数据上使用异质与同质模型重建的序列几乎相同,尽管具有显著的进化异质性.
- 使用来自具有不同突变效应的远距离相关蛋白质的模型对ASR的影响最小.
- 重建的差异主要发生在快速发展的地点或信号较弱的深层遗传节点.
结论:
- 祖先序列重建表明,当遗传信号强烈时,对现实的进化异质性的稳定性.
- 基因信号,而不是模型复杂性,是ASR准确性的主要驱动因素.
- 为了最大限度地提高ASR准确性,需要密集采样的对齐来增强遗传信号,而不是开发更复杂的模型.
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