在中性蛋白质进化过程中,与表观症相关的深陷和偶然性
Lisa Schmelkin1,2, Vincenzo Carnevale1,2,3, Allan Haldane3,4,5
1Institute for Genomics and Evolutionary Medicine, Temple University; Philadelphia, PA 19122, USA.
bioRxiv : the preprint server for biology
|January 27, 2025
概括
蛋白质进化与表达式显示出氨基酸偏好令人惊的保存,挑战了根深蒂固的概念. 这表明中性进化模型需要改进,以准确地反映蛋白质序列动态.
科学领域:
- 进化生物学是进化的生物学.
- 分子进化是分子进化的过程.
- 计算生物学是一种计算生物学.
背景情况:
- 基因相互作用影响健身的表观症 (epistasis) 复杂化了蛋白质序列的进化.
- 陷描述了氨基酸位点如何变得不那么耐受随着时间的推移而发生的变化,即使有中性替代.
- 现有的模型,比如波茨哈密尔顿模型,尽管目标是中立的场景,但经常模拟非中立的蛋白质进化.
研究的目的:
- 引入和测试一个新的模型,中性与表观性 (N×E),它将净化选择集成到中性进化模拟中.
- 通过epistasis在模拟中性条件下研究蛋白质进化中的固现象.
- 澄清分子时钟过度分散的驱动因素及其与表观和进化过程的关系.
主要方法:
- 开发含有净化选择的中性与表皮化 (N×E) 模型.
- 使用N×E模型对蛋白质进化进行模拟,以观察氨基酸位点动态.
- 分子时钟变化的分析及其与特定地点的表观学相关性的分析.
主要成果:
- N×E模型表明缺乏根深蒂固,保留了特定地点的氨基酸偏好,而不是生物现实的时间表.
- 广泛的残留物合并没有导致预期的特定地点偏好的损失.
- 分子时钟的过度分散归因于特定地点的速率变化,这是由血统中的表征驱动的,而不是历史的偶然性.
结论:
- 中性进化模型需要纳入净化选择,以准确模拟蛋白质序列动力学,避免明显的根深蒂固.
- 当与净化选择相结合时,表观学保持了特定地点的氨基酸偏好,挑战了以前关于固的假设.
- 这些发现表明,观察到的替代固和速率偶然性可能是非中性进化力的指标,例如适应.
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