Malmesbury, Wiltshire, SN16 0RN, UK.
Shrewsbury, Shropshire, SY3 8ZG, UK.
J Theor Biol. 2022 Nov 7;551-552:111244. doi: 10.1016/j.jtbi.2022.111244. Epub 2022 Aug 13.
In this paper we use simulation methods to investigate the proliferation of deletion mutations of mitochondrial DNA in neurons. We simulate three mtDNA proliferation mechanisms, namely, random drift, replicative advantage and vicious cycle. For each mechanism, we investigated the effect mutation rates have on neuron loss within a human host. We also compare heteroplasmy of each mechanism at mutation rates that yield the levels neuron loss that would be associated with dementia. Both random drift and vicious cycle predicted high levels of heteroplasmy, while replicative advantage showed a small number of dominant clones with a low background of heteroplasmy.
在本文中，我们使用模拟方法研究了线粒体 DNA 缺失突变在神经元中的增殖。我们模拟了三种 mtDNA 增殖机制，即随机漂移、复制优势和恶性循环。对于每种机制，我们研究了突变率对人类宿主中神经元丢失的影响。我们还比较了在导致与痴呆相关的神经元丢失水平的突变率下，每种机制的异质性。随机漂移和恶性循环都预测了高水平的异质性，而复制优势则显示出少数具有低背景异质性的优势克隆。
