Bochalis Eleftherios, Patsakis Michail, Chantzi Nikol, Mouratidis Ioannis, Chartoumpekis Dionysios V, Georgakopoulos-Soares Ilias
Institute for Personalized Medicine, Department of Biochemistry and Molecular Biology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.
Department of Internal Medicine, Division of Endocrinology, Medical School, University of Patras, Patras, Greece.
Protein Sci. 2025 Sep;34(9):e70241. doi: 10.1002/pro.70241.
The identification of succinct, universal fingerprints that enable the characterization of individual taxonomies can reveal insights into trait development. Here, we introduce taxonomic quasi-primes, peptide k-mer sequences that are exclusively present in a specific taxonomy and absent from all others. By analyzing 24,073 reference proteomes, we identified these unique peptides at the superkingdom, kingdom, and phylum ranks. These sequences exhibit remarkable uniqueness at six- and seven-amino-acid lengths. For instance, the seven-mer SAPNYCY is found in 98.11% of eukaryotic species, while being completely absent from archaeal, bacterial, and viral reference proteomes. Functional analysis demonstrated that taxonomic quasi-prime containing proteins are enriched for processes defining a lineage, such as synaptic signaling in Chordata. Structural analysis revealed that these peptides are preferentially located within proteins, participating directly in enzymatic active sites, mediating protein-protein interactions, and stabilizing ligand binding. Moreover, we show that in human proteins, highly conserved Chordata quasi-prime loci are 2.08-fold more likely to harbor pathogenic variants than surrounding regions, directly linking these evolutionary signatures to disease. This study establishes taxonomic quasi-primes as markers that illuminate evolutionary pathways and provide a powerful method for identifying functionally indispensable and disease-relevant loci, which warrant further therapeutic and diagnostic investigation.
识别简洁、通用的指纹图谱以实现对个体分类学的特征描述，能够揭示性状发育的见解。在此，我们引入分类学准素数，即特定分类学中独有的肽段k-mer序列，其他所有分类学中均不存在。通过分析24,073个参考蛋白质组，我们在超界、界和门的分类等级上鉴定出了这些独特的肽段。这些序列在六肽和七肽长度时表现出显著的独特性。例如，七肽SAPNYCY在98.11%的真核生物物种中存在，而在古菌、细菌和病毒参考蛋白质组中完全不存在。功能分析表明，含有分类学准素数的蛋白质在定义一个谱系的过程中富集，例如脊索动物中的突触信号传导。结构分析揭示，这些肽段优先位于蛋白质内部，直接参与酶活性位点，介导蛋白质-蛋白质相互作用，并稳定配体结合。此外，我们表明，在人类蛋白质中，高度保守的脊索动物准素数位点携带致病变异的可能性比周围区域高2.08倍，直接将这些进化特征与疾病联系起来。这项研究将分类学准素数确立为阐明进化途径的标记，并提供了一种强大的方法来识别功能上不可或缺和与疾病相关的位点，值得进一步进行治疗和诊断研究。
