Environmental Genomics & Systems Biology Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
Department of Molecular Biology, Genentech, South San Francisco, CA, USA.
Nat Rev Genet. 2022 Mar;23(3):182-194. doi: 10.1038/s41576-021-00424-x. Epub 2021 Nov 11.
Across the human genome, there are nearly 500 'ultraconserved' elements: regions of at least 200 contiguous nucleotides that are perfectly conserved in both the mouse and rat genomes. Remarkably, the majority of these sequences are non-coding, and many can function as enhancers that activate tissue-specific gene expression during embryonic development. From their first description more than 15 years ago, their extreme conservation has both fascinated and perplexed researchers in genomics and evolutionary biology. The intrigue around ultraconserved elements only grew with the observation that they are dispensable for viability. Here, we review recent progress towards understanding the general importance and the specific functions of ultraconserved sequences in mammalian development and human disease and discuss possible explanations for their extreme conservation.
在人类基因组中，有近 500 个“超保守”元件：至少 200 个连续核苷酸的区域，在老鼠和大鼠基因组中完全保守。值得注意的是，这些序列中的大多数是非编码的，许多可以作为增强子，在胚胎发育过程中激活组织特异性基因表达。从 15 年前首次描述以来，它们的极端保守性既令基因组学和进化生物学领域的研究人员着迷，也让他们感到困惑。随着观察到这些元件对于生存能力并非不可或缺，围绕超保守元件的研究兴趣进一步增长。在这里，我们综述了理解超保守序列在哺乳动物发育和人类疾病中的一般重要性和具体功能方面的最新进展，并讨论了它们极端保守性的可能解释。
