插入-删除事件在预测二次结构的蛋白质区域中被耗尽
Yi Yang1, Matthew V Braga1, Matthew D Dean1
1Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089, USA.
Genome biology and evolution
|May 12, 2024
概括
蛋白质编码基因中的插入删除 (indels) 在二级结构中被避免. 这表明自然选择不利于可能破坏蛋白质功能和稳定性的细胞.
科学领域:
- 进化生物学是进化的生物学.
- 人口遗传学 人口遗传学
- 基因组学就是基因组学.
- 蛋白质结构 蛋白质结构
背景情况:
- 了解自然选择如何对新突变产生作用,在进化生物学中至关重要.
- 插入-删除 (indel) 事件是遗传变异的关键来源.
- 和蛋白质二次结构之间的关系还不太清楚.
研究的目的:
- 为了测试蛋白质编码区域中的indels随机发生与蛋白质二次结构相关的假设.
- 为了研究选择对不同类型的二次结构中的内分分布的影响.
- 为了比较具有不同有效种群大小的物种之间在物种间的选择效率.
主要方法:
- 在 11,444 个来自老鼠,老鼠,人类,黑猩猩和狗基因组的序列对齐中识别了indels.
- 使用AlphaFold2深度学习模型预测蛋白质二次结构 (α螺旋,β链,曲,转).
- 量化的indel与预测的二次结构重叠,并分析了人类基因组中的indel频率.
主要成果:
- 在蛋白质的二次结构中,Indels的代表性不足 (54%低于预期),特别是在稳定的β链.
- 在没有预测的二次结构的地区,Indels被丰富了 (比预期增加155%).
- 在二级结构中对体的选择在动物中比灵长类更强,与有效种群大小相关.
- 非同义词的替换在次要结构中也较少,但不如indels.
- 人类基因组分析显示,与外部结构相比,二级结构内的indels的频率明显较低.
结论:
- 相互重叠的蛋白质二次结构被选择,可能是由于蛋白质三级结构和功能的破坏.
- 这些发现支持自然选择在塑造基于功能约束的动物进化中的作用.
- 动物和灵长类动物之间的选择效率差异与人口遗传预测一致.
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