Falk Martin J, Zhou Leon, Matsubara Yoshiya J, Husain Kabir, Szostak Jack W, Murugan Arvind
ArXiv. 2025 Aug 29:arXiv:2508.21806v1.
Modern life largely transmits genetic information from mother to daughter through the duplication of single physically intact molecules that encode information. However, copying an extended molecule requires highly processive copying machinery and high fidelity that scales with the genome size to avoid the error catastrophe. Here, we explore these fidelity requirements in an alternative architecture, the virtual circular genome, in which no one physical molecule encodes the full genetic information. Instead, information is encoded and transmitted in a collective of overlapping and interacting segments. Using a model experimental system of a complex mixture of DNA oligos that can partly anneal and extend off each other, we find that mutant oligomers are suppressed relative to a model without collective encoding. Through simulations and theory, we show that this suppression of mutants can be explained by competition for productive binding partners. As a consequence, information can be propagated robustly in a virtual circular genome even if the mutation rate is above the error catastrophe for a physically intact genome.
现代生活主要通过对编码信息的单个物理完整分子进行复制,将遗传信息从母亲传递给女儿。然而,复制一个长分子需要高度连续的复制机制和与基因组大小相匹配的高保真度,以避免错误灾难。在这里,我们在一种替代架构——虚拟环状基因组中探索这些保真度要求,在这种架构中,没有一个物理分子编码完整的遗传信息。相反,信息在一组重叠且相互作用的片段中进行编码和传递。使用一个由DNA寡核苷酸复杂混合物组成的模型实验系统,这些寡核苷酸可以部分相互退火并延伸,我们发现相对于没有集体编码的模型,突变寡聚物受到了抑制。通过模拟和理论分析,我们表明这种对突变体的抑制可以通过对有效结合伙伴的竞争来解释。因此,即使突变率高于物理完整基因组的错误灾难阈值,信息也可以在虚拟环状基因组中稳健地传播。