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

科学探究的两个目标是了解特征是如何发展和进化的。事实证明，对于基因组庞大、发育过程复杂的动物物种来说，这些目标很难实现。本项目将以果蝇D. melanogaster的雄性黑腹色素沉积模式作为性状发育的模型，并以具有不同色素沉积的亲缘物种为模型，了解雄性色素沉积的起源和多样性。为了确定哪些基因的使用或基因的使用在这种色素沉着多样性的途径中发生了变化，将研究具有祖先（D. willistoni）和修改（D. auraria）雄性色素沉着模式的物种中负责黑胃色素沉着的基因网络。对于具有不同用途的基因，将采用方法来发现和表征导致其变异的基因部分。这些修饰基因部分的重要性将通过将黑腹菌序列植入这两个研究较少的物种的基因组来检验。总的来说，这个项目将推动模式和新兴模式物种的遗传研究的极限，从而产生一种进化动物特征的最具洞察力的遗传特征。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各种人员，并通过创建、组织和主持一个对发育和进化遗传学有共同兴趣的科学家的虚拟会议来加速科学进步。动物形态是通过基因调控网络（grn）的运作而发展的，该网络涉及大量的反式调控因子、转录因子和信号通路，它们控制着性状构建实现器基因表达的空间、时间甚至性别特异性模式。这些基因表达模式源于GRN转录因子与其直接靶基因的顺式调控元件（CREs）结合位点的相互作用。由于许多反式调节基因和实现基因比它们调节的性状更古老，性状进化是通过改变这些祖先基因的使用而发生的。这个项目的首要目标是了解一个性状是如何通过改变GRN的反式调控基因和实现基因而出现和被修改的。在实验中可驯化的动物模型物种和密切相关的新兴模式物种中，快速进化性状的GRN的进化将被检查。本研究将重点研究雄性特异性腹部色素沉积模式是如何在黑腹果蝇谱系中出现的，以及它是如何在montium谱系中被修改的。在第一个目标中，将绘制黑腹龙GRN中反式调节因子的宽度，并确定哪些基因在具有祖先和修饰性状表型的物种中具有保守或进化的表达。第二个目标将确定反式调控因子和实现因子基因表达是如何通过CRE进化而进化的。第三个目标将通过在新兴模式物种中进行的基因工程直接测试GRN修饰的表型后果。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.