Incorporating antagonistic pleiotropy into models for molecular replicators.
Incorporating antagonistic pleiotropy into models for molecular replicators.
复制标题
将拮抗多效性纳入分子复制子模型。
DOI：
10.1016/j.biosystems.2020.104333
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Tower J
中科院分区：
文献类型：
--
作者：
Qu T;Calabrese P;Singhavi P;Tower J
在现代细胞中，由DNA组成的染色体基因编码多亚基蛋白/RNA复合物，催化染色体和细胞的复制。一种流行的生命起源理论认为，生命的早期阶段涉及一种称为复制因子的自我复制大分子，这种大分子可以被认为是能够自我复制的基因。关于人类和其他生物衰老的遗传学，一个流行的理论是拮抗多效性，它假设一个基因在一种情况下是有益的，在另一种情况下是有害的。我们之前报道过，分子复制子概念的简单性促进了两种涉及拮抗多效性的简单模型的产生。本文提出了第三种模型，每一种模型都改进了时间变量的定义。计算机模拟用于计算假设的双亚基复制子（AB）的增殖，当两个亚基(B)中的一个表现出拮抗多效性，导致B不稳定的优势。在模型1中，B的不稳定性产生了自由的A亚基，这反过来刺激了其他AB复制子的活性。在模型2中，B丢失，有时被更活跃的突变形式B '所取代。在模型3中，B被损坏并失去活性，其不稳定性允许它被新的B所取代。对于每个模型，确定了B的不稳定性有害的条件，以及B的不稳定性有益的条件。结果与拮抗多效性促进分子不稳定性和系统复杂性的假设一致，并为衰老与进化联系的模型提供了进一步的支持。
In modern cells, chromosomal genes composed of DNA encode multi-subunit protein/RNA complexes that catalyze the replication of the chromosome and cell. One prevailing theory for the origin of life posits an early stage involving self-replicating macromolecules called replicators, which can be considered genes capable of self-replication. One prevailing theory for the genetics of aging in humans and other organisms is antagonistic pleiotropy, which posits that a gene can be beneficial in one context, and detrimental in another context. We previously reported that the conceptual simplicity of molecular replicators facilitates the generation of two simple models involving antagonistic pleiotropy. Here a third model is proposed, and each of the three models is presented with improved definition of the time variable. Computer simulations were used to calculate the proliferation of a hypothetical two-subunit replicator (AB), when one of the two subunits (B) exhibits antagonistic pleiotropy, leading to an advantage for B to be unstable. In model 1, instability of B yields free A subunits, which in turn stimulate the activity of other AB replicators. In model 2, B is lost and sometimes replaced by a more active mutant form, B′. In model 3, B becomes damaged and loses activity, and its instability allows it to be replaced by a new B. For each model, conditions were identified where instability of B was detrimental, and where instability of B was beneficial. The results are consistent with the hypothesis that antagonistic pleiotropy can promote molecular instability and system complexity, and provide further support for a model linking aging and evolution.