保持从人类到斑马鱼的RET调节功能,没有序列相似性
Shannon Fisher1, Elizabeth A Grice, Ryan M Vinton
1McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. sfisher@jhmi.edu
Science (New York, N.Y.)
|March 25, 2006
概括
进化序列保护有助于识别调节性DNA. 然而,许多功能性非编码序列,特别是在RET基因中,可能仅仅通过相似性搜索就会错过.
科学领域:
- 基因组学就是基因组学.
- 发展生物学 发展生物学
- 进化生物学 进化生物学
背景情况:
- 进化序列保存是识别功能非编码监管元素的常用方法.
- RET原瘤基因在神经峰发育中起着至关重要的作用,并与各种癌症有关.
研究的目的:
- 通过转基因测试,研究 ret/RET locus 中的 teleost 和哺乳动物非编码序列的功能能力.
- 确定序列相似性方法是否充分捕捉所有功能性监管元素.
主要方法:
- 在斑马鱼中使用了基于转子子的转基因测试.
- 评估了斑马鱼 (teleost) 和人类 (哺乳动物) RET loci. 的保存非编码序列的调节活性.
- 监测报告者基因表达,以评估位置特异性调节.
主要成果:
- 大多数来自视网位的非编码序列驱动了记者基因表达,特别是在斑马鱼中.
- 许多远程传送序列显示了重叠的监管控制,表明复杂的监管网络.
- 大多数人类RET非编码序列也在斑马鱼中指导了ret特定表达.
- 即使在序列相似性较低的地区,也发现了功能性调节元素.
结论:
- 转基因测试揭示了重要的功能非编码序列信息,仅凭序列相似性无法检测.
- 在脊椎动物中保存的非编码元素可以保留保存的调节功能.
- 目前对序列保存的依赖可能低估了功能性非编码DNA的程度,特别是对于像RET.这样的基因.
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