Molecular Evolution of the Nuclear Factor (Erythroid-Derived 2)-Like 2 Gene Nrf2 in Old World Fruit Bats (Chiroptera: Pteropodidae).
Molecular Evolution of the Nuclear Factor (Erythroid-Derived 2)-Like 2 Gene Nrf2 in Old World Fruit Bats (Chiroptera: Pteropodidae).
复制标题
旧世界果蝠（翼手目：翼手目）核因子（红系衍生 2）样 2 基因 Nrf2 的分子进化
DOI：
10.1371/journal.pone.0146274
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Pan YH
中科院分区：
文献类型：
--
作者：
Yin Q;Zhu L;Liu D;Irwin DM;Zhang S;Pan YH
哺乳动物发展了抗氧化系统来抵御日常生活中的氧化损伤。酶促抗氧化剂和低分子量抗氧化剂（LMWAs）构成抗氧化系统的主要部分。核因子（红细胞衍生2）样2（Nrf2，由Nrf2基因编码）是一个中央转录调节因子，调节转录，许多抗氧化酶。食果蝙蝠吃大量含有高水平LMWAs（如维生素C）的水果，因此，与食虫蝙蝠相比，对LMWAs的依赖可能会大大减少对抗氧化酶的需求。因此，食果蝙蝠可能由于大量摄入饮食抗氧化剂而减少了对Nrf2功能的需求。为了测试Nrf2基因是否在食果蝙蝠中经历了宽松的进化，我们从16种蝙蝠中获得了Nrf2序列，包括4种旧世界果蝠（狐蝠科）和1种新世界果蝠（叶口科）。我们的分子进化分析揭示了作用于Nrf2基因的选择压力的变化，并确定了7个特定的氨基酸取代发生在祖先谱系上，导致旧大陆果蝠。进行了生化实验，以检查旧世界果蝠中的Nrf2，并表明由Nrf2调节的过氧化氢酶的量在旧世界果蝠的大脑，心脏和肝脏中显着降低，尽管旧世界果蝠中的Nrf2蛋白水平较高。计算预测表明，这七个氨基酸替换中的三个可能对Nrf2功能有害。因此，研究结果表明，Nrf2基因可能经历了放松约束在旧大陆果蝠，但我们不能排除积极选择的可能性。我们的研究提供了关于食果蝙蝠中Nrf2基因的分子适应性的第一个数据，以补偿其水果饮食中LWMA水平的增加。
Mammals developed antioxidant systems to defend against oxidative damage in their daily life. Enzymatic antioxidants and low molecular weight antioxidants (LMWAs) constitute major parts of the antioxidant systems. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2, encoded by the Nrf2 gene) is a central transcriptional regulator, regulating transcription, of many antioxidant enzymes. Frugivorous bats eat large amounts of fruits that contain high levels of LMWAs such as vitamin C, thus, a reliance on LMWAs might greatly reduce the need for antioxidant enzymes in comparison to insectivorous bats. Therefore, it is possible that frugivorous bats have a reduced need for Nrf2 function due to their substantial intake of diet-antioxidants. To test whether the Nrf2 gene has undergone relaxed evolution in fruit-eating bats, we obtained Nrf2 sequences from 16 species of bats, including four Old World fruit bats (Pteropodidae) and one New World fruit bat (Phyllostomidae). Our molecular evolutionary analyses revealed changes in the selection pressure acting on Nrf2 gene and identified seven specific amino acid substitutions that occurred on the ancestral lineage leading to Old World fruit bats. Biochemical experiments were conducted to examine Nrf2 in Old World fruit bats and showed that the amount of catalase, which is regulated by Nrf2, was significantly lower in the brain, heart and liver of Old World fruit bats despite higher levels of Nrf2 protein in Old World fruit bats. Computational predictions suggest that three of these seven amino acid replacements might be deleterious to Nrf2 function. Therefore, the results suggest that Nrf2 gene might have experienced relaxed constraint in Old World fruit bats, however, we cannot rule out the possibility of positive selection. Our study provides the first data on the molecular adaptation of Nrf2 gene in frugivorous bats in compensation to the increased levels of LWMAs from their fruit-diet.