Katikaneni Anushka, Lowe Craig B
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA; University Program in Genetics and Genomics, Duke University, Durham, NC 27708, USA.
Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA; University Program in Genetics and Genomics, Duke University, Durham, NC 27708, USA.
Curr Opin Genet Dev. 2025 Feb;90:102279. doi: 10.1016/j.gde.2024.102279. Epub 2024 Nov 26.
It is not currently understood how much of human evolution is due to modifying existing functional elements in the genome versus forging novel elements from nonfunctional DNA. Many early experiments that aimed to assign genetic changes on the human lineage to their resulting phenotypic change have focused on mutations that modify existing elements. However, a number of recent studies have highlighted the potential ease and importance of forging novel gene regulatory elements from nonfunctional sequences on the human lineage. In this review, we distinguish gene regulatory element novelty from innovation. We propose definitions for these terms and emphasize their importance in studying the genetic basis of human uniqueness. We discuss why the forging of novel regulatory elements may have been less emphasized during the previous decades, and why novel regulatory elements are likely to play a significant role in both human adaptation and disease.
目前尚不清楚人类进化中有多少是由于对基因组中现有的功能元件进行修饰，又有多少是源于从无功能的DNA中塑造新的元件。许多早期旨在将人类谱系中的基因变化与其产生的表型变化联系起来的实验，都集中在修饰现有元件的突变上。然而，最近的一些研究强调了从人类谱系中的无功能序列塑造新的基因调控元件的潜在简易性和重要性。在这篇综述中，我们区分了基因调控元件的新颖性和创新性。我们提出了这些术语的定义，并强调了它们在研究人类独特性的遗传基础中的重要性。我们讨论了为什么在过去几十年中对新调控元件的塑造可能较少受到重视，以及为什么新调控元件可能在人类适应和疾病中都发挥重要作用。
