Department of Molecular and Biomedical Sciences, J. Stefan Institute, 1000 Ljubljana, Slovenia.
Department of Biochemistry, Molecular and Structural Biology, J. Stefan Institute, 1000 Ljubljana, Slovenia.
Int J Mol Sci. 2023 Jul 21;24(14):11761. doi: 10.3390/ijms241411761.
Peptidases of the papain family play a key role in protein degradation, regulated proteolysis, and the host-pathogen arms race. Although the papain family has been the subject of many studies, knowledge about its diversity, origin, and evolution in Eukaryota, Bacteria, and Archaea is limited; thus, we aimed to address these long-standing knowledge gaps. We traced the origin and expansion of the papain family with a phylogenomic analysis, using sequence data from numerous prokaryotic and eukaryotic proteomes, transcriptomes, and genomes. We identified the full complement of the papain family in all prokaryotic and eukaryotic lineages. Analysis of the papain family provided strong evidence for its early diversification in the ancestor of eukaryotes. We found that the papain family has undergone complex and dynamic evolution through numerous gene duplications, which produced eight eukaryotic ancestral paralogous C1A lineages during eukaryogenesis. Different evolutionary forces operated on C1A peptidases, including gene duplication, horizontal gene transfer, and gene loss. This study challenges the current understanding of the origin and evolution of the papain family and provides valuable insights into their early diversification. The findings of this comprehensive study provide guidelines for future structural and functional studies of the papain family.
木瓜蛋白酶家族的肽酶在蛋白质降解、调控蛋白水解和宿主-病原体军备竞赛中发挥着关键作用。尽管木瓜蛋白酶家族已经成为许多研究的主题，但关于其在真核生物、细菌和古菌中的多样性、起源和进化的知识是有限的；因此，我们旨在解决这些长期存在的知识空白。我们通过对来自众多原核生物和真核生物蛋白质组、转录组和基因组的序列数据进行系统基因组学分析，追踪了木瓜蛋白酶家族的起源和扩张。我们确定了所有原核生物和真核生物谱系中木瓜蛋白酶家族的完整组成。对木瓜蛋白酶家族的分析为其在真核生物祖先中的早期多样化提供了强有力的证据。我们发现，通过大量基因复制，木瓜蛋白酶家族经历了复杂和动态的进化，在真核生物发生过程中产生了 8 个真核祖先同源 C1A 谱系。不同的进化力量作用于 C1A 肽酶上，包括基因复制、水平基因转移和基因丢失。这项研究挑战了当前对木瓜蛋白酶家族起源和进化的理解，并为其早期多样化提供了有价值的见解。这项全面研究的结果为木瓜蛋白酶家族的结构和功能研究提供了指导。
