非中性同名突变在推断选择对非同名突变的影响
Aina Martinez I Zurita1, Christopher C Kyriazis2, Kirk E Lohmueller1,3,2
1Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, USA.
bioRxiv : the preprint server for biology
|February 19, 2024
概括
对同名突变的选择可以扭曲对非同名突变的适应性效应 (DFE) 分布的估计. 进化遗传学的这种偏见可以通过使用准确的人口参数来纠正,而不是从同名变体推断出来的.
科学领域:
- 进化遗传学的进化遗传学
- 人口遗传学 人口遗传学
- 分子进化的分子进化.
背景情况:
- 适应性效应的分布 (DFE) 量化了新突变对生殖适应性的影响,这是进化遗传学的关键参数.
- 目前的方法通过首先从同义变异中估计人口参数来推断非同义突变的DFE,假设中立性.
- 新出现的证据表明同义突变也可能受到选择的影响,这可能违反了这种中立性假设.
研究的目的:
- 调查作用于同名突变的选择是否会影响DFE对非同名突变的推断.
- 评估非建模选择对同名变异对人口参数估计和随后的DFE推断的影响.
主要方法:
- 模拟了使用SLiM对同名突变的各种选择模型.
- 使用Fit∂a∂i,一种标准计算方法推断非同义突变的DFE.
- 在不同选择场景下对同名变体进行DFE和人口参数推断的比较.
主要成果:
- 对同名变体的选择导致对最近的人口增长的推断不准确.
- 在特定条件下,这种偏差导致DFE估计中的高度有害的非同义突变比例膨胀.
- 当使用正确的人口参数而不是从选定的同名变体中获得的参数时,对DFE推断的不利影响得到了缓解.
结论:
- 对同名突变的不计入选择可以显著扭曲DFE对非同名突变的下游推断.
- 准确的人口参数估计对于可靠的DFE推断至关重要,强调需要考虑在同义地点进行选择.
- 这项研究强调了对同名变异进行选择建模的重要性,以避免基本进化遗传参数的偏差.
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