The distribution of fitness effects (DFE) defines how new mutations spread through an evolving population. The ratio of non-synonymous to synonymous mutations (dN/dS) has become a popular method to detect selection in somatic cells. However the link, in somatic evolution, between dN/dS values and fitness coefficients is missing. Here we present a quantitative model of somatic evolutionary dynamics that determines the selective coefficients of individual driver mutations from dN/dS estimates. We then measure the DFE for somatic mutant clones in ostensibly normal oesophagus and skin. We reveal a broad distribution of fitness effects, with the largest fitness increases found for TP53 and NOTCH1 mutants (proliferative bias 1–5%). This study provides the theoretical link between dN/dS values and selective coefficients in somatic evolution, and measures the DFE of mutations in human tissues.

中文翻译：

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通过将克隆动力学与dN / dS比值相结合来测量体细胞进化中适应性效应的分布

适应性效应（DFE）的分布定义了新突变如何在不断发展的种群中传播。非同义突变与同义突变的比率（dN / dS）已成为检测体细胞选择的一种流行方法。但是，在体细胞进化中，dN / dS值与适应性系数之间的联系丢失了。在这里，我们提出了一种体细胞进化动力学的定量模型，该模型确定了来自dN / dS估计值的单个驾驶员突变的选择性系数。然后，我们测量表面正常食管和皮肤中的体细胞突变体克隆的DFE。我们揭示了健身效果的广泛分布，其中TP53和NOTCH1突变体（增殖偏倚1-5％）的健身增加幅度最大。这项研究提供了dN / dS值与体细胞进化中选择系数之间的理论联系，