基因清除和Neoave新陈代谢和寿命的演变
Deanna Ng1, Judy Pawling1, James W Dennis2
1Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
The Journal of biological chemistry
|November 2, 2023
概括
现代鸟类通过清除与分支链氨基酸 (BCAA) 运输和氧化相关的基因而进化,可能改善能量和寿命. 这种基因转移可能为人类健康和衰老提供了洞察力.
科学领域:
- 代谢调节和进化生物学
- 衰老和细胞能量学的分子机制.
- 比较基因组学和生理适应的比较.
背景情况:
- 蛋白质体的维护依赖于氧化酸化 (ATP) 和减轻氧化损伤,这些过程随着年龄的增长而下降.
- SLC3A2促进分支链氨基酸 (BCAA) 运输和囊进口以合成谷氨,影响肌肉耐力和衰老.
- 较高的BCAA水平与胰岛素耐药性和哺乳动物的寿命缩短有关.
研究的目的:
- 研究与新陈代谢途径相关的现代鸟类 (Neoaves) 的进化遗传适应.
- 探索基因清除和重复在Neoaves有关能量和氧化应激的功能后果.
- 确定Neoaves中潜在的分子重新连接,这些可能会为人类健康和长寿策略提供信息.
主要方法:
- 对Neoaves与其他鸟类群体和哺乳动物中的基因含量进行比较基因组分析.
- 根据基因丢失 (例如,SLC3A2,BCAT2) 和获取 (例如,SLC16A3,SLC7A9) 的推断功能转移.
- 假设从观察到的遗传变化中得出的代谢和生理后果,引用了像Lotka的最大功率原理这样的既有理论.
主要成果:
- 新生菌对参与BCAA运输 (SLC7A5家族) 和氧化 (BCAT2) 的基因进行了显著的净化.
- 在Neoaves中,基因重复包括运输体 (SLC16A3,SLC7A9) 和糖化酶 (MGAT4B,MGAT4C),这表明氨基酸和氧化应激代谢发生了改变.
- 这些遗传修饰似乎有利于减少BCAA氧化,增加转化为脂质,并增强氧化应激缓解.
结论:
- 鱼的进化轨迹涉及大量的基因简化,以优化能量,特别是飞行.
- 在Neoaves中观察到的遗传适应,包括降低BCAA代谢和增强的抗氧化能力,可能有助于它们独特的生理特征.
- 对Neoaves分子适应性的进一步研究可能会揭示人类衰老和代谢疾病的新型治疗点.
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