Tracing the origin and diversification of a morphological trait through transcriptional regulators and their target genes

通过转录调节因子及其靶基因追踪形态性状的起源和多样化

• 批准号: 2211833
• 负责人: Thomas Williams
• 金额: $ 103.65万
• 依托单位: University of Dayton
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2211833&HistoricalAwards=false
• 关键词: Tracing; origin; diversification; morphological; trait

Two goals of scientific inquiry are to understand how traits develop and evolve. These goals have proven difficult to reach for animal species with vast genomes and ones that undergo complex developmental processes. This project will use the pattern of male melanic abdomen pigmentation that develops for the fruit fly species D. melanogaster as a model for a trait’s development, and related species with differing pigmentation as models to understand how male pigmentation originated and diversified. In order to determine which gene’s use or genes’ uses have changed in route to this pigmentation diversity, the network of genes responsible for melanogaster pigmentation will be studied in species with the ancestral (D. willistoni) and modified (D. auraria) pattern of male pigmentation. For genes with differing uses, approaches will be utilized to find and characterize the parts of genes responsible for their variation. The importance of these modified gene parts will be tested by engineering melanogaster sequences into the genomes of these two less well-studied species. Collectively, this project will push the limits of genetic investigation in model and emerging-model species, resulting in one of the most insightful genetic characterizations of an evolving animal trait. This project will result in numerous broader impacts, such as the refinement of bioinformatic and online resources for genetics research, training of diverse personnel in genetics and related disciplines, and hastening scientific progress by the creation, organization, and hosting of a virtual meeting for scientists with a shared interest on the genetics of development and evolution. Animal morphology develops through the operation of Gene Regulatory Networks (GRNs) that involve a plethora of trans-regulators, transcription factors and signaling pathways, which control the spatial, temporal, and even sex-specific patterns of trait-building realizator gene expression. These patterns of gene expression emerge from GRN transcription factors interacting with binding sites in the cis-regulatory elements (CREs) of their direct target genes. Since many trans-regulators and realizator genes are older than the traits they regulate, trait evolution occurs through changes in the uses of these ancestral genes. This project’s overarching goal is to understand how a trait emerged and was modified by changes to a GRN’s trans-regulators and realizator genes. The evolution of a GRN for a rapidly evolving trait present in an experimentally tractable animal model species, and closely-related emerging model species will be examined. The proposed studies will focus on how the male-specific pattern of abdominal pigmentation emerged in the fruit fly lineage of D. melanogaster and how it was modified in the montium lineage. In the first Aim, the breadth of trans-regulators in the D. melanogaster GRN will be mapped, and determine which of these genes have conserved or evolved expressions in species with the ancestral and modified trait phenotypes. The second aim will determine how trans-regulator and realizator gene expressions evolved through CRE evolution. The third aim will directly test the phenotypic consequences of GRN modifications through genetic engineering performed in emerging model species.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.

科学研究的两个目标是了解特征是如何发展和进化的。事实证明，对于拥有大量基因组和经历复杂发育过程的动物物种来说，这些目标很难实现。这个项目将使用果蝇种黑腹雄性色素沉着的模式作为性状发育的模型，以及具有不同色素沉着的相关物种作为模型，以了解雄性色素沉着是如何起源和多样化的。为了确定哪一个或哪些基因的用途在导致这种色素多样性的途径上发生了变化，我们将研究具有男性色素沉积祖先(D.willistoni)和改良(D.auaria)模式的物种中负责黑色素沉着的基因网络。对于具有不同用途的基因，将利用方法来寻找和表征导致其变异的基因部分。这些修改过的基因部分的重要性将通过将黑素基因序列工程到这两个研究较少的物种的基因组中来检验。总体而言，该项目将推动模式物种和新兴模式物种的遗传研究的极限，从而产生对进化中的动物特征最有洞察力的遗传特征之一。该项目将产生许多更广泛的影响，例如完善遗传学研究的生物信息学和在线资源，培训遗传学和相关学科的不同人员，并通过创建、组织和主办一个关于发展和进化遗传学的共同兴趣的科学家虚拟会议来加速科学进步。动物的形态是通过基因调控网络(GRN)的运作而发展起来的，GRN涉及过多的反式调节因子、转录因子和信号通路，它们控制着特征构建实现者基因表达的空间、时间甚至性别特异性模式。这些基因表达模式是由GRN转录因子与其直接靶基因的顺式调控元件(CRE)中的结合位点相互作用而产生的。由于许多反式调节基因和实现基因比它们所调节的特征更古老，因此特征进化是通过改变这些祖先基因的用途来进行的。这个项目的首要目标是了解一个性状是如何出现的，并被GRN的反式调节基因和实现基因的变化所改变。将研究在实验上易驯化的动物模式物种和密切相关的新兴模式物种中存在的快速进化特征的GRN的进化。拟议的研究将集中在雄性特有的腹部色素沉着模式如何出现在黑腹果蝇的谱系中，以及它如何在单胞体谱系中被修改。在第一个目标中，我们将绘制黑腹果蝇GRN中反式调节基因的广度图，并确定这些基因中哪些基因在具有祖先和修改的性状表型的物种中保持或进化了表达。第二个目标将确定反式调节因子和实现因子基因的表达如何通过Cre进化而进化。第三个目标将通过在新兴模式物种中进行基因工程来直接测试GRN修改的表型后果。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

JEZB special issue on animal gene regulatory network evolution

JEZB动物基因调控网络进化特刊

• DOI: 10.1002/jez.b.23186
• 发表时间: 2023
• 期刊: Journal of Experimental Zoology Part B: Molecular and Developmental Evolution
• 作者: Williams, Thomas M.;Rebeiz, Mark
• 通讯作者: Rebeiz, Mark