Evolution of Gene Regulation through small RNA-mediated neofunctionalisation.

通过小 RNA 介导的新功能化进行基因调控的进化。

• 批准号: BB/S009256/1
• 负责人: Enrico Coen
• 金额: $ 90.12万
• 依托单位: John Innes Centre
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2019
• 资助国家: 英国
• 起止时间: 2019 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FS009256%2F1
• 关键词: Evolution; Gene; Regulation; through; small

The genetic makeup of every plant or animal comprises many thousands of genes, raising the question of where genes come from. A major source is the process of "neofunctionalization", whereby a gene becomes duplicated and one of the copies acquires a new function. This process is critical for the evolution of biological diversity and provides variation important for breeding or genetic engineering. Two types of neofunctionalisation have been traditionally described: changes in regions coding for proteins (C-NF), and changes in regions regulating where and when a gene is switched on (R-NF). Recent discoveries have raised the possibility of a third type, which we call small RNA-mediated neofunctionalisation (S-NF). S-NF involves mirror-image duplications of a gene which leads to the production of regulatory molecules, small RNAs, which inhibit another gene's activity. In this way a gene may adopt a new regulatory role. We have recently obtained evidence for S-NF contributing to the evolution of flower colour differences between species of snapdragon, Antirrhinum. In the longer term, some S-NF inverted duplications may become shorter and produce fewer small RNAs, giving rise to microRNA genes. The aim of this proposal is to test the idea that S-NF provides a natural mechanism of broad significance, complementing R-NF and C-NF, for creating new genes and refining gene activity during evolution.We will integrate several approaches to test this idea. First, we will use advances in DNA sequencing, allowing us to define genome sequence variation across a range of different plant species. Based on these findings, we will be able to map the origin, evolution and diversification of S-NF duplications and clarify their relation to microRNAs. Second, we will use genetic analysis, whereby individuals are crossed and progeny analysed, to separate the contribution of particular S-NF genes. Third, we will investigate how S-NF genes exert their effects by measuring their activity, and that of their targets, in different tissues and regions. Fourth, we will use phylogenetics, whereby evolutionary trees for genes and genomes may be constructed, to allow likely paths evolution has taken to be defined. Fifth, we will use population genomics, whereby the frequencies of genetic variants can be measured in natural populations, to infer which genes are likely under selection. Sixth, we will use transgenic approaches, introducing S-NF into species by genetic engineering, to investigate and evaluate how it can be used to influence and refine gene activity patterns. We will apply these approaches to snapdragon species and their relatives. S-NF has already been established in this system in relation to flower colour, which provides a convenient and sensitive way to detect variation in patterns of gene activity. Moreover, the ability to inter-cross snapdragon species that differ widely in colour or other traits, allows the genetic contribution of genes to be readily followed. Engineering and breeding flower colours is also a test bed for evaluating the contributions of S-NF. Taken together our studies should provide new insights into how new gene activities arise and the contribution of S-NF to evolution and breeding.

每一种植物或动物的基因组成都由成千上万的基因组成，这就提出了基因从何而来的问题。一个主要来源是“新功能化”过程，即基因被复制，其中一个拷贝获得新的功能。这一过程对生物多样性的进化至关重要，并为育种或基因工程提供了重要的变异。传统上描述了两种类型的新功能化：蛋白质编码区域的变化（C-NF）和调节基因何时何地开启的区域的变化（R-NF）。最近的发现提出了第三种类型的可能性，我们称之为小RNA介导的新功能化（S-NF）。S-NF涉及一个基因的镜像复制，这导致产生抑制另一个基因活性的调节分子，小RNA。通过这种方式，一个基因可能会采取新的调节作用。我们最近获得的证据S-NF有助于金鱼草，金鱼草物种之间的花色差异的演变。从长远来看，一些S-NF反向重复可能会变得更短，产生更少的小RNA，从而产生microRNA基因。本提案的目的是验证S-NF提供了一种具有广泛意义的自然机制，补充了R-NF和C-NF，用于在进化过程中创造新基因和改善基因活性。我们将整合几种方法来验证这一想法。首先，我们将利用DNA测序的进展，使我们能够定义一系列不同植物物种的基因组序列变异。基于这些发现，我们将能够绘制S-NF重复的起源，进化和多样化，并阐明它们与microRNA的关系。第二，我们将使用遗传分析，即个体杂交和后代分析，以分离特定S-NF基因的贡献。第三，我们将研究S-NF基因如何发挥其作用，通过测量他们的活动，他们的目标，在不同的组织和地区。第四，我们将使用遗传学，从而可以构建基因和基因组的进化树，以允许定义进化所采取的可能路径。第五，我们将使用群体基因组学，即可以在自然群体中测量遗传变异的频率，以推断哪些基因可能受到选择。第六，我们将使用转基因方法，通过基因工程将S-NF引入物种，以研究和评估它如何用于影响和改善基因活性模式。我们将把这些方法应用于金鱼草物种及其亲属。S-NF已经在该系统中建立了花的颜色，这提供了一个方便和灵敏的方法来检测基因活性模式的变化。此外，能够在颜色或其他性状差异很大的金鱼草物种之间进行杂交，可以很容易地跟踪基因的遗传贡献。花色工程和育种也是评估S-NF贡献的试验平台。总之，我们的研究应该提供新的见解，新的基因活动如何出现和S-NF的进化和育种的贡献。

项目成果

Engaging new audiences with imaging and microscopy

通过成像和显微镜吸引新受众

• DOI: 10.1242/dev.199942
• 发表时间: 2021
• 期刊: Development
• 影响因子: 4.6
• 作者: Barresi, Michael J.;Coen, Enrico;Kugler, Elisabeth;Shuda, Jamie;Sung, Derek C.
• 通讯作者: Sung, Derek C.