撰文丨王聪 编辑丨王多鱼 排版丨水成文 同义突变 （ Synonymous mutation ） 是指编码 DNA 序列发生变化但不改变所编码的氨基酸，因此也就 不会改变蛋白质序列，这是由于 遗传密码系统的 简并性 （不止一个密码子对应同一个氨基酸） 。人们长 期以来一直认为，绝大多数同意突变都是无意义的，只有少数例外。 值得注意的是，近年来有研究显示，某些同义突变可能会影响转录和转录后过程。还有体外研究显示， 同 义突变 可能会改变 RNA 结构并影响其功能。尽管这些发现表明同义变化在细胞功能和生物体适应性方面 发挥着作用，但在多细胞生物中，关于同义突变影响生物性状或相关作用模式的遗传证据仍然很少。 2025 年 7 月 1 日， 中国农业科学院蔬菜花卉研究所 杨学勇 研究员、 中国农业科学院（深圳）农业基因 组研究所 黄三文 院士、 英国约翰英纳斯研究中心 丁一倞 研究员团队与河南大学、青岛农业大学、芝加哥 大学的研究人员合作，在国际顶尖学术期刊 Cell 上发表了题为： Recessive epistasis of a synonymous mutation confers cucumber domes ...

Core Insights - The article highlights significant research advancements published in the journal Cell, with a focus on studies led by Chinese scholars, covering topics such as organoid development, vascular dementia mechanisms, autoimmune disease treatments, and the role of synonymous mutations in cucumber domestication [2][4][8][12][17]. Group 1: Highly Vascularized Lung and Gut Organoids - A collaborative study from Cincinnati Children's Hospital and UCLA successfully constructed highly vascularized lung and gut organoids using human induced pluripotent stem cells (iPSCs), providing a platform for studying organ development and disease [4]. Group 2: Mechanisms of Vascular Dementia Repair - Research from UCLA identified key signaling pathways involved in brain repair for vascular dementia, specifically the CD39-A3AR pathway, and demonstrated that the A3AR agonist Piclidenoson could promote brain tissue repair and restore memory and gait functions [8]. Group 3: LAG-3/TCR Dual Antibody for Autoimmune Diseases - A study from NYU and Chinese institutions revealed a novel mechanism of LAG-3 receptor activation, which could lead to the development of dual-specific T cell inhibitory antibodies targeting LAG-3 and TCR, offering new therapeutic avenues for autoimmune diseases [12][13]. Group 4: Synonymous Mutations in Cucumber Domestication - Research from the Chinese Academy of Agricultural Sciences demonstrated that synonymous mutations can regulate important traits in cucumber domestication through epitranscriptomic mechanisms, challenging traditional views and suggesting new strategies for crop improvement [17].

Core Viewpoint - The article discusses the significance of synonymous mutations in genetic research, particularly their role in cucumber domestication through epitranscriptomic regulation, challenging traditional views on these mutations [2][3]. Group 1: Research Findings - The study published in the journal Cell demonstrates that synonymous mutations can regulate important traits in cucumber by altering m6A modifications and mRNA structural conformations [2][3]. - The research identifies two closely linked genes, YTH1 and ACS2, that interact epistatically to influence cucumber fruit length [5][9]. - A specific synonymous mutation, 1287C>T in the ACS2 gene, is identified as a pathogenic mutation that disrupts m6A methylation and alters RNA structure, leading to changes in fruit length [6][9]. Group 2: Genetic Mechanisms - The YTH1 gene encodes an m6A reader protein, while the ACS2 gene encodes a rate-limiting enzyme for ethylene synthesis in plants, both of which are crucial for cucumber domestication [5][9]. - The study reveals that the wild-type cucumber's ACS2 1287C leads to m6A modification and a loose RNA structure, while the cultivated cucumber's ACS2 1287T results in a compact RNA structure, affecting protein levels and fruit length [6][9].

Core Viewpoint - The article discusses the emerging understanding of synonymous mutations in human cells, challenging the traditional view of these mutations as neutral and highlighting their potential impact on cellular adaptability and disease [2][5][6]. Group 1: Research Background - A study by a team from the University of Michigan suggested that synonymous mutations in yeast may not be neutral and could affect cellular adaptability, reigniting interest in their biological effects [1]. - Previous research has linked a small number of synonymous mutations to human diseases, indicating their potential role as cancer drivers, but experimental confirmation remains limited [6]. Group 2: New Research Findings - A new study published by researchers from Peking University developed a high-throughput screening technology named PRESENT to investigate functional synonymous mutations in the human genome [4]. - The research utilized an advanced prime editing system (PEmax) to create a library targeting 3,644 human protein-coding genes, allowing for large-scale screening of synonymous mutations [7]. Group 3: Methodology and Tools - The study integrated single-cell screening methods with the PRESENT technology, termed DIRECTED-seq, to systematically evaluate the impact of identified synonymous mutations on gene expression [8]. - A specialized machine learning model called DS Finder was developed to analyze the effects of functional synonymous mutations on various biological processes, such as mRNA splicing and transcription [9][11]. Group 4: Key Findings - The research indicated that synonymous mutations exhibit different fitness effects compared to non-synonymous mutations, although their phenotypic distribution was similar to negative controls [9]. - The study identified that synonymous mutations could alter RNA folding and affect translation, with PLK1_S2 being a notable example, and combined screening data with predictive models to identify clinically relevant synonymous mutations [9].