Morenikeji Olanrewaju B, Thomas Bolaji N
Department of Biomedical Sciences, Rochester Institute of Technology, Rochester, NY, USA.
PeerJ. 2019 Jul 12;7:e7325. doi: 10.7717/peerj.7325. eCollection 2019.
The cluster differentiation gene (CD14) is a family of monocyte differentiating genes that works in conjunction with lipopolysaccharide binding protein, forming a complex with TLR4 or LY96 to mediate innate immune response to pathogens. In this paper, we used different computational methods to elucidate the evolution of CD14 gene coding region in 14 mammalian species. Our analyses identified leucine-rich repeats as the only significant domain across the CD14 protein of the 14 species, presenting with frequencies ranging from one to four. Importantly, we found signal peptides located at mutational hotspots demonstrating that this gene is conserved across these species. Out of the 10 selected variants analyzed in this study, only six were predicted to possess significant deleterious effect. Our predicted protein interactome showed a significant varying protein-protein interaction with CD14 protein across the species. This may be important for drug target and therapeutic manipulation for the treatment of many diseases. We conclude that these results contribute to our understanding of the CD14 molecular evolution, which underlays varying species response to complex disease traits.
簇分化基因(CD14)是一类单核细胞分化基因家族,它与脂多糖结合蛋白协同作用,与Toll样受体4(TLR4)或髓样分化蛋白2(LY96)形成复合物,介导对病原体的固有免疫反应。在本文中,我们使用了不同的计算方法来阐明14种哺乳动物物种中CD14基因编码区的进化情况。我们的分析确定富含亮氨酸重复序列是这14个物种的CD14蛋白中唯一显著的结构域,出现频率从1到4不等。重要的是,我们发现信号肽位于突变热点区域,表明该基因在这些物种中是保守的。在本研究分析的10个选定变体中,只有6个被预测具有显著的有害作用。我们预测的蛋白质相互作用组显示,不同物种中与CD14蛋白的蛋白质 - 蛋白质相互作用存在显著差异。这对于治疗许多疾病的药物靶点和治疗操作可能很重要。我们得出结论,这些结果有助于我们理解CD14的分子进化,它是不同物种对复杂疾病特征产生不同反应的基础。