Collaborative Research: cis-Regulatory architecture of color pattern convergence

合作研究：颜色模式融合的顺式监管架构

• 批准号: 2242864
• 负责人: Sean Mullen
• 金额: $ 71.58万
• 依托单位: Trustees of Boston University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2242864&HistoricalAwards=false
• 关键词: Collaborative; Research; cis; Regulatory; architecture

Understanding the origin and maintenance of biological diversity requires connecting patterns of genetic variation at the molecular level with morphological differences among individuals, populations, or species. Over the last decade, many examples of adaptive trait variation have been linked to developmental changes in gene expression. Regions of the genome that lie in between genes contain “regulatory elements” that regulate spatial and temporal patterns of gene expression. These regulatory regions are thought to play an essential role in trait adaptation. However, our understanding of the specific mechanisms through which regulatory elements have driven morphological diversification remains limited. Do changes involve a small number of elements with large effect, or many elements of minor effect? Do new gene expression patterns appear via origination of new elements, or changes in older ancestral elements? How do the functions of individual elements change? To what extent might some elements facilitate the convergence of traits across different linages? This project aims to address these questions. In doing so, it will decode some of the rules governing the structure, function, and evolution of regulatory elements. Specifically, the investigators will couple comparative biology with mechanistic studies of regulatory elements to understand the regulatory basis of repeated color pattern evolution in butterflies. The work will include public engagement at the Boston Science Museum. In addition, the work will develop strategies for increasing the recruitment of graduate students from historically underrepresented groups. Cis-regulatory elements (CREs) include promotors, enhancers, and silencers. These elements play an essential role in phenotypic evolution because they regulate patterns of gene expression during development. Despite recent progress in identifying and characterizing CREs responsible for adaptive trait variation, many questions remain. For example, what is the relationship between sequence divergence, the genomic architecture of transcription factor binding sites within CREs, and CRE function? Addressing these questions is complicated. CREs have been hypothesized to act as relatively independent modules controlling tissue-specific expression. However, growing evidence indicates that CRE mutations may have multiple downstream effects. Here, we propose to use the power of repeated evolution within a comparative framework to decode the rules governing CRE structure, function, and evolution. Our research addresses three primary questions. First, how is population-level sequence divergence responsible for wing pattern mimicry related to chromatin accessibility and patterns of gene expression in Limenitis butterflies? Second, to what extent does deep regulatory homology underlie repeated cases of convergent evolution across different phylogenetic timescales? Third, how do deeply ancestral vs. recently derived CREs contribute to color pattern evolution and convergence? We will answer these questions by identifying and functionally characterizing CREs controlling the expression of two genes, WntA and optix. These genes have been shown to underlie adaptive mimetic color pattern divergence within and between butterfly species. We will then leverage the widespread occurrence of convergent evolution across three butterfly genera to study broad-scale evolutionary patterns of CRE gain and loss. Ultimately, our results will shed light on how cis-regulatory elements arise, how they function to determine phenotype, and what rules govern their evolution.This project is co-funded by the Genetic Mechanisms program of the Molecular and Cellular Biosciences Division in the Biological Sciences Directorate.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

了解生物多样性的起源和维持需要在分子水平上将遗传变异的模式与个体、种群或物种之间的形态差异联系起来。在过去的十年中，许多适应性性状变异的例子都与基因表达的发育变化有关。位于基因之间的基因组区域包含调节基因表达的空间和时间模式的“调节元件”。这些调控区域被认为在性状适应中发挥重要作用。然而，我们对调控元件驱动形态多样化的具体机制的理解仍然有限。变更涉及的是影响大的少数要素，还是影响小的许多要素？新的基因表达模式是通过新元素的起源出现的，还是通过旧的祖先元素的变化出现的？单个元素的功能如何变化？在何种程度上，某些元素可以促进不同血统的性状趋同？本项目旨在解决这些问题。在这样做的过程中，它将解码一些规则的结构，功能和调控元件的演变。具体来说，研究人员将比较生物学与调控元件的机制研究相结合，以了解蝴蝶重复颜色模式进化的调控基础。这项工作将包括在波士顿科学博物馆的公众参与。此外，这项工作还将制定战略，增加从历来代表性不足的群体中招聘研究生。顺式调节元件（克雷斯）包括启动子、增强子和沉默子。这些元件在表型进化中发挥重要作用，因为它们调节发育过程中的基因表达模式。尽管最近在识别和表征负责适应性性状变异的克雷斯方面取得了进展，但仍存在许多问题。例如，序列差异、克雷斯内转录因子结合位点的基因组结构和CRE功能之间的关系是什么？解决这些问题是复杂的。克雷斯已被假设为控制组织特异性表达的相对独立的模块。然而，越来越多的证据表明，CRE突变可能具有多种下游效应。在这里，我们建议使用的权力，重复进化的比较框架内解码的规则，CRE的结构，功能和演变。我们的研究解决了三个主要问题。首先，如何是人口水平的序列分歧负责翼模式模仿相关的染色质可及性和模式的基因表达在Limenitis蝴蝶？第二，在多大程度上深调控同源性的基础上重复的情况下，跨越不同的系统发育时间尺度的趋同进化？第三，深层祖先与最近衍生的克雷斯如何有助于颜色模式的进化和收敛？我们将回答这些问题，确定和功能特性的克雷斯控制两个基因，WntA和Optix的表达。这些基因已被证明是蝴蝶物种内部和之间适应性模仿颜色模式分歧的基础。然后，我们将利用广泛发生的收敛进化在三个蝴蝶属研究大规模的进化模式的CRE的增益和损失。最终，我们的研究结果将揭示顺式调控元件是如何产生的，它们是如何起作用来决定表型的，以及它们的进化规律。这个项目是共同的-该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的评估被认为值得支持。影响审查标准。