小柯机器人

发育增强子具有密集且多效性的调控信息
2020-10-17 22:46

德国欧洲分子生物学实验室Justin Crocker、美国霍华德.休斯医学研究所David L. Stern等研究人员,合作揭示发育增强子中的密集且多效性的调控信息。 2020年10月14日,国际知名学术期刊《自然》在线发表了这一成果。

通过使用自动机器人流水线,研究人员调查了果蝇中发育增强子的无偏突变库。研究人员发现几乎所有的突变都改变了基因的表达,并且涉及到基因表达的参数(水平、位置和状态)。大多数突变的多效性效应可能会限制发育增强子的进化。
 
与这些观察结果一致,对各种果蝇幼虫的比较揭示了在由增强子影响的表型中存在明显的偏差。与以前已经认识到的相比,发育增强子可以编码更高密度的调控信息,从而对调控进化施加了限制。
 
据了解,基因调控的变化是许多表型进化的基础。 但是,由于大多数证据来自自然变异或有限的实验扰动,因此人们对调控进化潜力的理解是有偏见的。
 
附:英文原文

Title: Dense and pleiotropic regulatory information in a developmental enhancer

Author: Timothy Fuqua, Jeff Jordan, Maria Elize van Breugel, Aliaksandr Halavatyi, Christian Tischer, Peter Polidoro, Namiko Abe, Albert Tsai, Richard S. Mann, David L. Stern, Justin Crocker

Issue&Volume: 2020-10-14

Abstract: Changes in gene regulation underlie much of phenotypic evolution1. However, our understanding of the potential for regulatory evolution is biased, because most evidence comes from either natural variation or limited experimental perturbations2. Using an automated robotics pipeline, we surveyed an unbiased mutation library for a developmental enhancer in Drosophila melanogaster. We found that almost all mutations altered gene expression and that parameters of gene expression—levels, location, and state—were convolved. The widespread pleiotropic effects of most mutations may constrain the evolvability of developmental enhancers. Consistent with these observations, comparisons of diverse Drosophila larvae revealed apparent biases in the phenotypes influenced by the enhancer. Developmental enhancers may encode a higher density of regulatory information than has been appreciated previously, imposing constraints on regulatory evolution. A robotic pipeline is used to survey a library of mutations in a Drosphila gene enhancer, showing that most mutations altered gene expression and had widespread pleiotropic effects that are likely to constrain regulatory evolution.

DOI: 10.1038/s41586-020-2816-5

Source: https://www.nature.com/articles/s41586-020-2816-5

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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