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首页> 外文期刊>The FEBS journal >Analysis of the nicotinamide phosphoribosyltransferase family provides insight into vertebrate adaptation to different oxygen levels during the water-to-land transition
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Analysis of the nicotinamide phosphoribosyltransferase family provides insight into vertebrate adaptation to different oxygen levels during the water-to-land transition

机译:烟酰胺磷酸核糖基转移酶家族的分析提供了洞察脊椎动物在水到陆过渡过程中对不同氧水平的适应性

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摘要

One of the most important events in vertebrate evolutionary history is the water-to-land transition, during which some morphological and physiological changes occurred in concert with the loss of specific genes in tetrapods. However, the molecular mechanisms underlying this transition have not been well explored. To explore vertebrate adaptation to different oxygen levels during the water-to-land transition, we performed comprehensive bioinformatics and experimental analysis aiming to investigate the NAMPT family in vertebrates. NAMPT, a rate-limiting enzyme in the salvage pathway of NAD+ biosynthesis, is critical for cell survival in a hypoxic environment, and a high level of NAMPT significantly augments oxidative stress in normoxic environments. Phylogenetic analysis showed that NAMPT duplicates arose from a second round whole-genome duplication event. NAMPTA existed in all classes of vertebrates, whereas NAMPTB was only found in fishes and not tetrapods. Asymmetric evolutionary rates and purifying selection were the main evolutionary forces involved. Although functional analysis identified several functionally divergent sites during NAMPT family evolution, invitro experimental data demonstrated that NAMPTA and NAMPTB were functionally conserved for NAMPT enzymatic function in the NAD+ salvage pathway. Insitu hybridization revealed broad NAMPTA and NAMPTB expression patterns, implying regulatory functions over a wide range of developmental processes. The morpholino-mediated knockdown data demonstrated that NAMPTA was more essential than NAMPTB for vertebrate embryo development. We propose that the retention of NAMPTB in water-breathing fishes and its loss in air-breathing tetrapods resulted from vertebrate adaptation to different oxygen levels during the water-to-land transition.
机译:脊椎动物进化史上最重要的事件之一是水到土地的过渡,在此期间,某些形态和生理变化与四足动物中特定基因的丢失共同发生。然而,尚未很好地探索这种转变的分子机制。为了探索脊椎动物在水到陆过渡过程中对不同氧水平的适应性,我们进行了全面的生物信息学和实验分析,旨在研究脊椎动物中的NAMPT家族。 NAMPT是NAD +生物合成挽救途径中的限速酶,对于缺氧环境中的细胞存活至关重要,而高水平的NAMPT会在常氧环境中显着增加氧化应激。系统发育分析表明,NAMPT重复序列是由第二轮全基因组重复事件引起的。 NAMPTA存在于所有类型的脊椎动物中,而NAMPTB仅在鱼类中发现而不在四足动物中发现。不对称的进化速率和纯化选择是其中涉及的主要进化力量。尽管功能分析在NAMPT家族进化过程中发现了几个功能不同的位点,但体外实验数据表明NAMPTA和NAMPTB在NAD +挽救途径中在功能上保守NAMPT酶功能。原位杂交揭示了广泛的NAMPTA和NAMPTB表达模式,这意味着在广泛的发育过程中具有调控功能。吗啉代介导的基因敲除数据表明,NAMPTA比NAMPTB对于脊椎动物胚胎发育更重要。我们建议,NAMPTB在吸水鱼类中的保留及其在空气呼吸四足动物中的损失是由于脊椎动物从水到陆过渡过程中适应不同的氧气水平而导致的。

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