Dandage Rohan, Papkov Mikhail, Greco Brittany M, Pereira Vanessa, Fishman Dmytro, Friesen Helena, Wang Kyle, Styles Erin B, Kraus Oren, Grys Benjamin, Zapata Gerardo, Lefebvre Francois, Bourque Guillaume, Boone Charles, Andrews Brenda J, Parts Leopold, Kuzmin Elena
Department of Biology, Concordia University, Montreal, QC, Canada.
Centre for Applied Synthetic Biology, Centre for Structural and Functional Genomics, Concordia University, Montreal, QC, Canada.
iScience. 2025 May 27;28(7):112771. doi: 10.1016/j.isci.2025.112771. eCollection 2025 Jul 18.
Gene duplication is common across the Tree of Life and contributes to genomic robustness. In this study, we examined changes in the subcellular localization and abundance of proteins in response to the deletion of their paralogs originating from the whole-genome duplication event, which is a largely unexplored mechanism of functional divergence. We performed a systematic single-cell imaging analysis of protein dynamics and screened subcellular redistribution of proteins. We find that 20% of proteins exhibit redistribution, of which 1/3 relocalized and 1/2 changed in abundance. Paralogs showed dependency, whereby proteins required their paralog to maintain their endogenous abundance or localization, 2-fold more often than compensation. Network feature analysis suggested the importance of functional redundancy and rewiring of protein and genetic interactions underlying redistribution paralog response. Translation of alternate protein isoform emerged as a compensatory mechanism. This study provides insight into paralog retention and evolutionary forces that shape genomes.
基因复制在整个生命之树中很常见，并有助于基因组的稳健性。在本研究中，我们研究了蛋白质的亚细胞定位和丰度响应其源自全基因组复制事件的旁系同源基因缺失的变化，这是一种在很大程度上未被探索的功能分化机制。我们对蛋白质动力学进行了系统的单细胞成像分析，并筛选了蛋白质的亚细胞重新分布。我们发现20%的蛋白质表现出重新分布，其中1/3重新定位，1/2丰度发生变化。旁系同源基因表现出依赖性，即蛋白质需要其旁系同源基因来维持其内源性丰度或定位，这种情况比补偿情况多两倍。网络特征分析表明了功能冗余以及蛋白质和遗传相互作用重新连接在旁系同源基因响应重新分布中的重要性。可变蛋白质异构体的翻译成为一种补偿机制。这项研究为旁系同源基因保留以及塑造基因组的进化力量提供了见解。
