Data from: Stronger selective constraint on downstream genes in the oxidative phosphorylation pathway of cetaceans

The oxidative phosphorylation (OXPHOS) pathway is an efficient way to produce energy via adenosine triphosphate (ATP), which is critical for sustaining an energy supply for cetaceans in a hypoxic environment. Several studies have shown that natural selection may shape the evolution of the genes involved in OXPHOS. However, how network architecture drives OXPHOS protein sequence evolution remains poorly explored. Here, we investigated the evolutionary patterns of genes in the OXPHOS pathway across six cetacean genomes within the framework of a functional network. Our results show a negative correlation between the strength of purifying selection and pathway position. This result indicates that downstream genes were subjected to stronger evolutionary constraints than upstream genes, which may be due to the dual function of ATP synthase in the OXPHOS pathway. Additionally, there was a positive correlation between codon usage bias and omega (ω = dN/dS) and a negative correlation with synonymous substitution rate (dS), indicating that the stronger selective constraint on genes (with less biased codon usage) along the OXPHOS pathway is attributable to an increase in the rate of synonymous substitution. Surprisingly, there was no significant correlation between protein-protein interactions and the evolutionary estimates, implying that highly connected enzymes may not always show greater evolutionary constraints. Compared with that observed for terrestrial mammals, we found that the signature of positive selection detected in five genes (ATP5J, LHPP, PPA1, UQCRC1, UQCRQ) was cetacean-specific, reflecting the importance of OXPHOS for survival in hypoxic, aquatic environments.

氧化磷酸化（OXPHOS）通路是通过三磷酸腺苷（ATP）合成能量的高效途径，而ATP对于维持鲸类在低氧环境中的能量供给至关重要。多项研究表明，自然选择可能塑造了OXPHOS相关基因的演化历程。然而，网络架构如何驱动OXPHOS蛋白质序列的演化，目前仍缺乏深入探索。本研究基于功能网络框架，分析了6个鲸类基因组中OXPHOS通路基因的演化模式。研究结果显示，纯化选择强度与通路位置呈负相关，这表明下游基因所受的演化约束强于上游基因，该现象可能源于ATP合酶在OXPHOS通路中的双重功能。此外，密码子使用偏好性与ω值（ω = dN/dS，即非同义替换率与同义替换率的比值）呈正相关，而与同义替换率（dS）呈负相关，这说明OXPHOS通路上密码子使用偏好性较弱的基因所受的选择约束更强，这一特性可归因于同义替换率的升高。令人意外的是，蛋白质相互作用强度与演化估计参数之间未呈现显著相关性，这意味着连接度较高的酶类未必始终承受更强的演化约束。相较于陆生哺乳动物，本研究在5个基因（ATP5J、LHPP、PPA1、UQCRC1、UQCRQ）中检测到的正选择特征为鲸类所特有，这反映出OXPHOS通路对于鲸类在低氧水生环境中生存的关键意义。