发表机构
University of Torino; University of Padova; Max Planck Institute for the Physics of Complex Systems（都灵大学; 帕多瓦大学; 马克斯·普朗克复杂系统物理研究所）
机构由 AI 辅助整理，请以论文原文为准。AI 中文总结
本研究通过人类突变场分解，发现突变偏差主要由类平衡能量景观主导，并存在可复现的不可逆环流，指向甲基胞嘧啶脱氨等定向机制。
AI 中文摘要
DNA序列的进化可以被视为高维离散空间上的随机动力学，但尚不清楚经验性转移偏差何时可归结为有效能量景观，何时保留不可约的非平衡环流。人类情境依赖性突变概率提供了一个直接检验：局部情境中的每个单核苷酸替换都有一个反向替换，因此正向与反向概率比的对数定义了一个反对称场——人类突变场。我们表明该场具有主导的梯度分量和一个较小但可复现的旋度分量。利用七碱基人类种系替换概率，我们通过一个受约束仅预测能量差异的Siamese神经网络推断出一个有效的突变景观。该模型对留出突变的预测正向与反向对数比的相关性约为0.93，接近无约束预测参考值（0.948）和来自Hodge投影的经验可逆上限（约0.96）。尽管仅基于突变概率训练，推断出的景观在很大程度上恢复了长度至四的短词基因组组成和Chargaff反向互补对称性。偏离平衡结构揭示了一个微小但可检测的非平衡分量：一个违反Kolmogorov循环细致平衡条件的残余不可逆环流，在非洲、亚洲和欧洲人群中均可复现，并在CpG相关循环和CpG转换边中最强，与甲基胞嘧啶脱氨一致。这些结果给出了人类突变场的热力学分解：大多数突变偏差由与基因组组成对齐的局部类平衡能量景观组织，而残余环流指向特定的定向突变机制。
英文摘要
The evolution of DNA sequences can be viewed as stochastic dynamics on a high-dimensional discrete space, but it is unclear when empirical transition biases reduce to an effective energy landscape versus retain irreducible non-equilibrium circulation. Human context-dependent mutation probabilities offer a direct test: every single-nucleotide substitution in a local context has a reverse substitution, so the logarithm of the forward-to-reverse probability ratio defines an antisymmetric field-the human mutation field. We show this field has a dominant gradient component and a smaller but reproducible curl component. Using seven-base human germline substitution probabilities, we infer an effective mutational landscape with a Siamese neural network constrained to predict only energy differences. This model predicts forward-to-reverse log-ratios for held-out mutations with a correlation of about 0.93, close to both an unconstrained predictive reference (0.948) and the empirical reversible ceiling from Hodge projection (about 0.96). Although trained only on mutation probabilities, the inferred landscape largely recovers short-word genomic composition and Chargaff reverse-complement symmetry for sequences up to length four. Deviations from equilibrium structure reveal a small but detectable nonequilibrium component: a residual irreversible circulation violating the Kolmogorov cycle condition for detailed balance, reproducible across African, Asian, and European populations, and strongest in CpG-linked cycles and CpG-transition edges, consistent with methylcytosine deamination. These results give a thermodynamic decomposition of the human mutation field: most mutation bias is organized by a local equilibrium-like energy landscape aligned with genome composition, while the residual circulation points to specific directional mutational mechanisms.
Comments12 pages, 5 figures, 1 table
