揭示了人类和其他灵长类动物中孤儿载体SLC22A10的功能
Sook Wah Yee1, Luis Ferrández-Peral2, Pol Alentorn-Moron2
1Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA.
Nature communications
|May 23, 2024
概括
人类的SLC22A10是由于突变而导致的非功能转运器,与其运输性类固醇合体的大猿对应物不同. 这种功能损失发生在人类进化过程中,影响了类固醇平衡.
科学领域:
- 基因组学就是基因组学.
- 分子生物学分子生物学
- 进化生物学 进化生物学
背景情况:
- SLC22A10是一种孤儿输送器,其功能和基质特异性尚未确定.
- 了解它的作用对于阐明类固醇稳态和生物体发育至关重要.
研究的目的:
- 为了确定人类SLC22A10.10的基质特异性和功能特征.
- 为了研究SLC22A10在人类类动物中的功能演化轨迹.
主要方法:
- 使用绿色光蛋白 (GFP) 标记用于蛋白质定位研究.
- 在表达人类和大猿SLC22A10的细胞模型中进行了涉及基质吸收的功能测试.
- 进行了序列对齐和位点定向突变发生 (P220L) 以确定关键的功能残留物.
主要成果:
- 人类的SLC22A10,与大猿类的ortolog不同,未能定位到等离子体膜,缺乏运输功能.
- 大猿SLC22A10的正方体有效地运输雌醇-17β-葡萄化物.
- 在人体SLC22A10中,单个氨基酸替代 (在220位的Proline到Leucine) 恢复了膜局部化和运输功能.
- 古代人类基因组 (尼安德特人,丹尼索瓦人) 在220位拥有祖先的普罗林,这表明人类血统中的功能损失.
结论:
- 人类SLC22A10因固定P220突变而演变为伪基因,失去其传承性类固醇合体的祖先能力.
- 这种在SLC22A10中的进化性功能丧失对类固醇稳态和人类的发育有影响.
- 对比基因组学和功能研究对于理解载体进化和生物作用至关重要.
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