由有害突变引起的遗传补偿,但不是基因淘汰
Andrea Rossi1, Zacharias Kontarakis1, Claudia Gerri1
1Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
Nature
|July 14, 2015
概括
斑马鱼egfl7和vegfaa的基因突变触发了补偿基因网络,与基因淘汰不同. 这解释了为什么突变分子通常没有表型,而敲击导致严重的血管缺陷,揭示了关键的缓冲机制.
科学领域:
- 发展生物学 发展生物学
- 遗传学 遗传学 是一个
- 分子生物学分子生物学
背景情况:
- 细胞通过调节基因表达来适应环境变化.
- 基因剂量补偿机制对于维持细胞功能至关重要.
- 在模型生物体中观察到基因突变和基因淘汰之间的表型差异.
研究的目的:
- 调查遗传突变者和基因淘汰之间的表型差异的分子基础.
- 确定对功能丧失突变进行缓冲的补偿机制.
主要方法:
- 在斑马鱼中产生egfl7和vegfaa突变体.
- 突变动物和变态动物之间的蛋白质组和转录组的比较 (敲击).
- 对egfl7的CRISPR干扰的分析,以区分敲击和突变效应.
主要成果:
- egfl7突变体没有表现型,而egfl7形态体则表现出严重的血管缺陷.
- 不同于变形体,egfl7突变体表现出补偿性细胞外基因基因的上调.
- 维格法变异体调节维格法,这种现象在维格法变异体中没有见过.
- 导致严重缺陷的egfl7CRISPR干扰没有诱导补偿基因上调.
结论:
- 作为对基因突变的反应,一个补偿基因网络被激活,而不是转化或转录的淘汰.
- 这个网络缓冲有害突变,解释了一些突变体缺乏表型.
- 了解这些补偿机制对于解释遗传学研究和治疗干预措施至关重要.
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