Leukotriene signaling in the extinct human subspecies Homo denisovan and Homo neanderthalensis. Structural and functional comparison with Homo sapiens
Leukotriene signaling in the extinct human subspecies Homo denisovan and Homo neanderthalensis. Structural and functional comparison with Homo sapiens
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DOI：
10.1016/j.abb.2014.10.012
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发表时间：
2015-01-01
影响因子：
3.9
通讯作者：
Heydeck, Dagmar
中科院分区：
文献类型：
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作者：
Adel, Susan;Kakularam, Kumar Reddy;Heydeck, Dagmar
哺乳动物脂氧合酶（LOX）与细胞分化以及促炎和抗炎脂质介质的生物合成有关。尼安德特人基因组的初始草图序列（覆盖率为1.3倍）表明，由于必需蛋白质的表达似乎被破坏，因此在这个古老的人类亚种中存在白三烯信号传导缺陷。与此同时，高质量的基因组序列数据成为两个灭绝的人类亚种（H。尼安德特人（Neanderthalensis）和丹尼索瓦人（Homo denisovan）的发现以及人类1000基因组计划的完成，提供了一个描述人类基因组遗传变异性的全面数据库。为了这项研究，我们从相应的数据库中提取了所选的类花生酸相关基因（ALOX 5、ALOX 15、ALOX 12、ALOX 15 B、ALOX 12 B、ALOX 3、COX 1、COX 2、LTA 4H、LTC4S、ALOX 5AP、CYSLTR 1、CYSLTR 2、BLTR 1、BLTR 2）的核苷酸序列。与定点突变研究和结构建模的推导的氨基酸序列的比较表明，白三烯信号传导的主要酶和受体以及两个环氧合酶亚型在这两个灭绝的人类亚种中是完全功能性的。(C)2014爱思唯尔公司All rights reserved.
Mammalian lipoxygenases (LOXs) have been implicated in cell differentiation and in the biosynthesis of pro- and anti-inflammatory lipid mediators. The initial draft sequence of the Homo neanderthalensis genome (coverage of 1.3-fold) suggested defective leukotriene signaling in this archaic human subspecies since expression of essential proteins appeared to be corrupted. Meanwhile high quality genomic sequence data became available for two extinct human subspecies (H. neanderthalensis, Homo denisovan) and completion of the human 1000 genome project provided a comprehensive database characterizing the genetic variability of the human genome. For this study we extracted the nucleotide sequences of selected eicosanoid relevant genes (ALOX5, ALOX15, ALOX12, ALOX15B, ALOX12B, ALOXE3, COX1, COX2, LTA4H, LTC4S, ALOX5AP, CYSLTR1, CYSLTR2, BLTR1, BLTR2) from the corresponding databases. Comparison of the deduced amino acid sequences in connection with site-directed mutagenesis studies and structural modeling suggested that the major enzymes and receptors of leukotriene signaling as well as the two cyclooxygenase isoforms were fully functional in these two extinct human subspecies. (C) 2014 Elsevier Inc. All rights reserved.