Evolutionary features of ligands and their receptors via protein-protein interactions and essentiality in primates
Evolutionary features of ligands and their receptors via protein-protein interactions and essentiality in primates
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DOI：
10.1111/gtc.13006
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发表时间：
2023-01-14
期刊：
影响因子：
2.1
通讯作者：
Ito，Michihiko
中科院分区：
文献类型：
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作者：
Mawaribuchi，Shuuji;Haramoto，Yoshikazu;Ito，Michihiko
蛋白质进化速率与几个效应因子呈负相关，如表达水平、表达分布、蛋白质-蛋白质相互作用（PPI）和生存必要性。这些效应物可以表征由配体-受体结合介导的信号传导途径。然而，目前尚不清楚这些效应物是否是配体和受体的途径特异性进化的限制因素。为了阐明配体及其受体中的效应子与蛋白质进化（dN/dSratio）之间的关系，考虑到每个信号传导途径，我们使用15个灵长类序列研究了20个肽/蛋白质配体组及其受体组中的377个蛋白质。肽/蛋白质配体基团与其受体基团之间的dN/dS比值呈正相关，表明蛋白质的进化受其所属信号通路的影响。比较各信号通路，主要与发育和生长相关的配体和受体（FGF/Hedgehog/Notch/WNT组）dN/dS比值较低，PPI数较高，重要性较高，而主要与免疫过程相关的配体和受体（CSF/IFN/IL/TNF组）dN/dS比值较高，PPI数较低，重要性较低。大多数配体和受体表达水平较低，表达水平不是蛋白进化的制约因素。这些发现表明，PPI和必要性是表征配体和受体的途径特异性进化的限制因素。
Protein evolution rate is negatively correlated with several effectors, such as expression level, expression distribution, protein–protein interactions (PPIs), and essentiality for survival. These effectors can characterize the signaling pathways mediated by ligand‐receptor binding. However, it is unclear whether these effectors are constraining factors on the pathway‐specific evolution of ligands and receptors. To clarify the relation between the effectors and protein evolution (dN/dSratio) in ligands and their receptors considering each signaling pathway, we investigated 377 proteins in 20 peptide/protein ligand groups and their receptor groups using 15 primate sequences. ThedN/dSratios between peptide/protein ligand groups and their receptor groups were positively correlated, suggesting the protein evolution under the influence of signaling pathway to which they belong. Comparing each signaling pathway, ligands and receptors mainly related to development and growth (FGF/Hedgehog/Notch/WNT groups) showed lowerdN/dSratios, higher PPI numbers, and higher essentiality, whereas those mainly related to immune process (CSF/IFN/IL/TNF groups) showed higherdN/dSratios, lower PPI numbers, and lower essentiality. Most ligands and receptors were poorly expressed, and expression level was not a constraining factor on the protein evolution. These findings indicate that PPI and essentiality are constraining factors that characterize the pathway‐specific evolution of ligands and receptors.