古代的转录调节器可以很容易地发展出新的对智合作性
Kyle R Fowler1, Fredrick Leon1, Alexander D Johnson1,2
1TETRAD Graduate Program, Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94158.
概括
推动基因调节的新蛋白相互作用迅速演变,许多解决方案具有功能. 这项研究揭示了管理转录调节器合作性的演变的结构规则和约束.
科学领域:
- 进化生物学是进化的生物学.
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 细胞使用转录调节剂结合cis调节DNA进行基因表达控制.
- 监管机构之间的配对合作使复杂的基因调节和网络演变成为可能.
- 了解监管机构之间的合作相互作用的起源对于进化见解至关重要.
研究的目的:
- 研究Matα2和Mcm1.1之间的特定蛋白质-蛋白质相互作用的进化出现.
- 揭示规范转录监管机构合作关系发展的结构规则和约束.
主要方法:
- 深度突变扫描与合作基因表达的功能选择相结合.
- 为Matα2-Mcm1相互作用接口测试数百万种替代进化解决方案.
- 分析功能变体以确定新出现的结构和表观规则.
主要成果:
- 大约45%的随机序列与自然的Matα2-Mcm1相互作用一样或更好地起作用.
- 功能性溶液高度退化,允许不同的氨基酸化学成分.
- 观察到广泛的表观症,尽管有退化,但限制了进化成功.
结论:
- 转录调节者之间合作的出现并不完全取决于历史路径.
- 结构规则和表观局限性约束控制了基因调节中的蛋白质-蛋白质相互作用的演变.
- 这项工作为转录网络可塑性和新型相互作用的演变提供了机械的见解.
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