论文标题

最密集的生存是衰老中线粒体突变的膨胀

Survival of the densest accounts for the expansion of mitochondrial mutations in ageing

论文作者

Insalata, Ferdinando, Hoitzing, Hanne, Aryaman, Juvid, Jones, Nick S.

论文摘要

已缺失的线粒体DNA(mtDNA)分子的扩展与衰老有关,尤其是在骨骼肌纤维中。三十年来,其机制一直尚不清楚。先前的帐户为删除分配了复制优势,但是有证据表明单元可以选择性地删除有缺陷的mtDNA。我们提出了一个空间模型,该模型没有复制优势,而是通过突变体和噪声增强密度的组合,可以产生与实验数据一致的波速扩展突变的波浪,这与基于复制优势的标准模型不同。我们提供了一个公式,该公式可以预测波速随拷贝数下降,与实验数据一致。至关重要的是,即使突变体优先消除,我们的模型也会产生突变体的行进波。通过这一示例证明了噪声,密度和空间结构如何影响肌肉老化,我们介绍了最浓度的随机生存的机制,即复制优势的替代性,它可能是其他现象的基础,例如利他主义的进化。

The expansion of deleted mitochondrial DNA (mtDNA) molecules has been linked to ageing, particularly in skeletal muscle fibres; its mechanism has remained unclear for three decades. Previous accounts assigned a replicative advantage to the deletions, but there is evidence that cells can, instead, selectively remove defective mtDNA. We present a spatial model that, without a replicative advantage, but instead through a combination of enhanced density for mutants and noise, produces a wave of expanding mutations with wave speed consistent with experimental data, unlike a standard model based on replicative advantage. We provide a formula that predicts that the wave speed drops with copy number, in agreement with experimental data. Crucially, our model yields travelling waves of mutants even if mutants are preferentially eliminated. Justified by this exemplar of how noise, density and spatial structure affect muscle ageing, we introduce the mechanism of stochastic survival of the densest, an alternative to replicative advantage, that may underpin other phenomena, like the evolution of altruism.

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