Epigenetic gambling and epigenetic drift as an antagonistic pleiotropic mechanism of aging
Epigenetic gambling and epigenetic drift as an antagonistic pleiotropic mechanism of aging
复制标题
DOI：
10.1111/j.1474-9726.2009.00515.x
复制
发表时间：
2009-12-01
期刊：
影响因子：
7.8
通讯作者：
Martin, George M.
中科院分区：
文献类型：
--
作者：
Martin, George M.
P>；几代生物老年学家一直对他们的实验模式生物在种内寿命的显著差异感到困惑，尽管他们尽了一切努力控制基因和环境。最有说服力的例子来自对野生型秀丽线虫在无菌悬浮培养中生长时的生命表研究。虽然核和线粒体的体细胞突变和‘热力学噪音’可能导致这种寿命差异，但我提出了一个额外的假设机制，一种可能已经进化为表型变异的机制，该机制可能先于减数分裂重组的进化。我认为，细胞基因表达的随机变化(细胞表观遗传赌博或赌注对冲)演变为一种适应机制，以确保群体成员在不可预测的环境挑战下生存。一旦被激活，它可能会在该群体的所有成员中导致渐进性表观遗传差异(表观遗传漂移)。因此，虽然特定的基因表达模式一旦启动，就会适应种群中早期生殖个体的子集，但我预测，持续的表观遗传漂移将导致不同的病理生理起点和模式--也许这是衰老表型发生中拮抗多效性基因作用的另一个例子。这一假说的弱点是，我们目前还没有一个可信的分子机制来解释表观遗传表达的假定遗传‘随机者’，特别是它的‘设置’可能对给定物种进化的生态做出反应。然而，我提供了一些实验方法来寻找难以捉摸的表观遗传赌徒(S饰)。
P>Generations of biogerontologists have been puzzled by the marked intraspecific variations in lifespan of their experimental model organisms despite all efforts to control both genotype and environment. The most cogent example comes from life table studies of wild-type Caenorhabditis elegans when grown in suspension cultures using axenic media. While nuclear and mitochondrial somatic mutations and 'thermodynamic noise' likely contribute to such lifespan variegations, I raise an additional hypothetical mechanism, one that may have evolved as a mechanism of phenotypic variation which could have preceded the evolution of meiotic recombination. I suggest that random changes in cellular gene expression (cellular epigenetic gambling or bet hedging) evolved as an adaptive mechanism to ensure survival of members of a group in the face of unpredictable environmental challenges. Once activated, it could lead to progressive epigenetic variegation (epigenetic drift) amongst all members of the group. Thus, while particular patterns of gene expression would be adaptive for a subset of reproductive individuals within a population early in life, once initiated, I predict that continued epigenetic drift will result in variable onsets and patterns of pathophysiology - perhaps yet another example of antagonistic pleiotropic gene action in the genesis of senescent phenotypes. The weakness of this hypothesis is that we do not currently have a plausible molecular mechanism for the putative genetic 'randomizer' of epigenetic expression, particularly one whose 'setting' may be responsive to the ecology in which a given species evolves. I offer experimental approaches, however, to search for the elusive epigenetic gambler(s).