Herbert Alan
Discovery, InsideOutBio , Charlestown, MA, USA.
Biol Lett. 2025 Jan;21(1):20240635. doi: 10.1098/rsbl.2024.0635. Epub 2025 Jan 22.
This paper is focused on the origins of the contemporary genetic code. A novel explanation is proposed for how the mapping of nucleotides in DNA to amino acids in proteins arose that derives from repeat nucleotide sequences able to form alternative nucleic acid structures (ANS), such as the unusual left-handed Z-DNA, triplex, G-quadruplex and I-motif conformations. The scheme identifies sequence-specific contacts that map ANS repeats to dipeptide polymers (DPS). The stereochemistry required naturally evolves into a non-overlapping, triplet code for mapping nucleotides to amino acids. The ANS/DPS complexes form a simple, genetically transmitted, self-templating, autonomously replicating collection of 'tinkers' for Nature to evolve. Tinkers have agency and promote their own synthesis by forming catalytic scaffolds with metals, further enhancing their capabilities. Initial support for the model is provided by computational models built with AlphaFold3. The predictions made are properly falsifiable with the currently available methodology.
本文聚焦于当代遗传密码的起源。针对DNA中的核苷酸如何映射到蛋白质中的氨基酸这一问题,提出了一种新颖的解释,该解释源于能够形成替代核酸结构(ANS)的重复核苷酸序列,例如不寻常的左手Z-DNA、三链体、G-四链体和I-基序构象。该方案确定了将ANS重复序列映射到二肽聚合物(DPS)的序列特异性接触。所需的立体化学自然演变成一种用于将核苷酸映射到氨基酸的非重叠三联体密码。ANS/DPS复合物形成了一组简单的、可遗传传递的、自我模板化的、自主复制的“修补匠”集合,供自然进化。修补匠具有能动性,并通过与金属形成催化支架来促进自身的合成,进一步增强其能力。使用AlphaFold3构建的计算模型为该模型提供了初步支持。所做的预测可以用当前可用的方法进行适当的证伪。