Department of Biochemistry and Molecular Biology, University of Chicago, United States of America.
Department of Physiology, Anatomy & Genetics, University of Oxford, United Kingdom.
Prog Biophys Mol Biol. 2021 Oct;165:140-152. doi: 10.1016/j.pbiomolbio.2021.04.004. Epub 2021 Apr 30.
The common belief that the neo-Darwinian Modern Synthesis (MS) was buttressed by the discoveries of molecular biology is incorrect. On the contrary those discoveries have undermined the MS. This article discusses the many processes revealed by molecular studies and genome sequencing that contribute to evolution but nonetheless lie beyond the strict confines of the MS formulated in the 1940s. The core assumptions of the MS that molecular studies have discredited include the idea that DNA is intrinsically a faithful self-replicator, the one-way transfer of heritable information from nucleic acids to other cell molecules, the myth of "selfish DNA", and the existence of an impenetrable Weismann Barrier separating somatic and germ line cells. Processes fundamental to modern evolutionary theory include symbiogenesis, biosphere interactions between distant taxa (including viruses), horizontal DNA transfers, natural genetic engineering, organismal stress responses that activate intrinsic genome change operators, and macroevolution by genome restructuring (distinct from the gradual accumulation of local microevolutionary changes in the MS). These 21st Century concepts treat the evolving genome as a highly formatted and integrated Read-Write (RW) database rather than a Read-Only Memory (ROM) collection of independent gene units that change by random copying errors. Most of the discoverers of these macroevolutionary processes have been ignored in mainstream textbooks and popularizations of evolutionary biology, as we document in some detail. Ironically, we show that the active view of evolution that emerges from genomics and molecular biology is much closer to the 19th century ideas of both Darwin and Lamarck. The capacity of cells to activate evolutionary genome change under stress can account for some of the most negative clinical results in oncology, especially the sudden appearance of treatment-resistant and more aggressive tumors following therapies intended to eradicate all cancer cells. Knowing that extreme stress can be a trigger for punctuated macroevolutionary change suggests that less lethal therapies may result in longer survival times.
普遍认为新达尔文综合理论(MS)得到了分子生物学发现的支持,但实际上这种观点是不正确的。相反,这些发现破坏了 MS。本文讨论了分子研究和基因组测序揭示的许多有助于进化的过程,但这些过程都超出了 20 世纪 40 年代制定的 MS 的严格范围。MS 的核心假设已经被分子研究所否定,包括 DNA 本质上是一个忠实的自我复制者、遗传信息从核酸单向传递到其他细胞分子、“自私 DNA”的神话以及存在不可穿透的魏斯曼屏障将体细胞和生殖细胞分隔开等。现代进化理论的基本过程包括共生、遥远分类群之间的生物圈相互作用(包括病毒)、水平 DNA 转移、自然遗传工程、激活内在基因组改变操作子的生物体应激反应,以及通过基因组重排进行的宏观进化(与 MS 中逐渐积累的局部微观进化变化不同)。这些 21 世纪的概念将进化中的基因组视为一个高度格式化和集成的读写(RW)数据库,而不是一个只读存储器(ROM)集合,其中独立的基因单元通过随机复制错误发生变化。正如我们详细记录的那样,这些宏观进化过程的大多数发现者在主流教科书和进化生物学的通俗化中被忽视了。具有讽刺意味的是,我们表明,从基因组学和分子生物学中出现的积极进化观点更接近达尔文和拉马克的 19 世纪思想。细胞在应激下激活进化基因组变化的能力可以解释肿瘤学中一些最负面的临床结果,尤其是在意图根除所有癌细胞的治疗后,治疗抵抗性和更具侵袭性的肿瘤突然出现。了解极端应激可以成为突发宏观进化变化的触发因素表明,致死性较低的治疗可能会导致更长的生存时间。