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非达尔文分子生物学

Non-Darwinian Molecular Biology.

作者信息

Palazzo Alexander F, Kejiou Nevraj S

机构信息

Department of Biochemistry, University of Toronto, Toronto, ON, Canada.

出版信息

Front Genet. 2022 Feb 16;13:831068. doi: 10.3389/fgene.2022.831068. eCollection 2022.

Abstract

With the discovery of the double helical structure of DNA, a shift occurred in how biologists investigated questions surrounding cellular processes, such as protein synthesis. Instead of viewing biological activity through the lens of chemical reactions, this new field used biological information to gain a new profound view of how biological systems work. Molecular biologists asked new types of questions that would have been inconceivable to the older generation of researchers, such as how cellular machineries convert inherited biological information into functional molecules like proteins. This new focus on biological information also gave molecular biologists a way to link their findings to concepts developed by genetics and the modern synthesis. However, by the late 1960s this all changed. Elevated rates of mutation, unsustainable genetic loads, and high levels of variation in populations, challenged Darwinian evolution, a central tenant of the modern synthesis, where adaptation was the main driver of evolutionary change. Building on these findings, Motoo Kimura advanced the neutral theory of molecular evolution, which advocates that selection in multicellular eukaryotes is weak and that most genomic changes are neutral and due to random drift. This was further elaborated by Jack King and Thomas Jukes, in their paper "Non-Darwinian Evolution", where they pointed out that the observed changes seen in proteins and the types of polymorphisms observed in populations only become understandable when we take into account biochemistry and Kimura's new theory. Fifty years later, most molecular biologists remain unaware of these fundamental advances. Their adaptionist viewpoint fails to explain data collected from new powerful technologies which can detect exceedingly rare biochemical events. For example, high throughput sequencing routinely detects RNA transcripts being produced from almost the entire genome yet are present less than one copy per thousand cells and appear to lack any function. Molecular biologists must now reincorporate ideas from classical biochemistry and absorb modern concepts from molecular evolution, to craft a new lens through which they can evaluate the functionality of transcriptional units, and make sense of our messy, intricate, and complicated genome.

摘要

随着DNA双螺旋结构的发现,生物学家研究围绕细胞过程(如蛋白质合成)问题的方式发生了转变。这个新领域不再通过化学反应的视角来看待生物活性,而是利用生物信息来获得关于生物系统如何运作的全新深刻认识。分子生物学家提出了新一代研究人员难以想象的新型问题,比如细胞机制如何将遗传的生物信息转化为像蛋白质这样的功能分子。这种对生物信息的新关注也为分子生物学家提供了一种将他们的发现与遗传学和现代综合理论所发展的概念联系起来的方法。然而,到了20世纪60年代末,一切都改变了。突变率升高、遗传负荷不可持续以及种群中的高变异水平,对现代综合理论的核心支柱——达尔文进化论提出了挑战,在该理论中适应是进化变化的主要驱动力。基于这些发现,木村资生提出了分子进化的中性理论,该理论主张多细胞真核生物中的选择作用微弱,大多数基因组变化是中性的,是由随机漂变导致的。杰克·金和托马斯·朱克斯在他们的论文《非达尔文进化》中进一步阐述了这一理论,他们指出,只有当我们考虑生物化学和木村的新理论时,蛋白质中观察到的变化以及种群中观察到的多态性类型才变得可以理解。五十年后,大多数分子生物学家仍然没有意识到这些根本性的进展。他们的适应主义观点无法解释从能够检测极其罕见生化事件的新强大技术中收集到的数据。例如,高通量测序经常检测到几乎整个基因组产生的RNA转录本,但每千个细胞中存在不到一个拷贝,而且似乎缺乏任何功能。分子生物学家现在必须重新纳入经典生物化学的观点,并吸收分子进化的现代概念,以打造一个新的视角,通过这个视角他们可以评估转录单元的功能,并理解我们杂乱、复杂且纷繁的基因组。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c889/8888898/a420d34d73c9/fgene-13-831068-g001.jpg

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