Causes and Consequences of Size Evolution in Drosophila melanogaster

果蝇体型进化的原因和后果

基本信息

批准号：
9269111
负责人：
JOHN E POOL
金额：
$ 27.97万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2019-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9269111
关键词：
Adult African Altitude Attention Biological Biological Models Body Size Buffers Candidate Disease Gene Cell Count Cell Cycle Cell Nucleus Cell Proliferation Cell Size Cells Clustered Regularly Interspaced Short Palindromic Repeats Code Collection Complement Data Detection Development Diabetes Mellitus Disease Drosophila genus Drosophila melanogaster Epithelial Ethiopia Ethiopian Evolution Foundations Frequencies Gene Mutation Gene Targeting Gene Transfer Techniques Generations Genes Genetic Genetic Variation Genetic study Genomic Segment Genomics Haplotypes Human Inbreeding Insulin Knowledge Laboratories Learning Link Malignant Neoplasms Mediating Medical Medical Research Methods Molecular Muscle Muscle Cells Muscle Fibers Mutagenesis Mutation Natural Selections Nature Organism Phenotype Play Ploidies Population Population Genetics Property Quantitative Genetics Quantitative Trait Loci Recording of previous events Research Role Sampling Scanning Signal Pathway System Testing Tissues Transgenic Organisms Variant Veins Wing Work base experimental study fly gene function gene replacement genetic analysis genetic resource genome-wide genomic data insulin signaling interest novel novel strategies public health relevance simulation stem tool trait

项目摘要

DESCRIPTION (provided by applicant): This research investigates the genetic basis, cellular mechanisms, and developmental consequences of body and wing size evolution in a newly discovered high altitude population of Drosophila melanogaster which represents the largest known flies of this species. This trait offers the unique opportunity to relate a biologically important phenotypic difference to its underlying cellular mechanisms and to specific genes and mutations responsible for this change. The Drosophila system offers a range of advantages to study adaptive evolution at the genetic level, from population genomic data to transgenic tools. Results will increase our knowledge of the polygenicity of adaptation and the properties of causative variants (e.g. coding vs. regulatory; new mutations vs. standing genetic variation). This research integrates biological subdisciplines to reveal cell-level mechanisms (e.g. cell proliferation and somatic ploidy) responsible for phenotypic evolution. It also takes a rare look a the potential influence of adaptive evolution on developmental stability. This work will reveal how evolution has altered the function of genes involved in insulin signaling and the cell cycle without harmful consequences to the organism - findings that may ultimately prove relevant for research on cancer, diabetes, and other medical conditions. 1. Conduct a genome-wide search for genes that play a role in body size evolution. Confirm their effects and test causative mutations using transgenesis. A novel QTL mapping method will localize causative genes to the ~100kb scale. A new population genetic statistic will reveal genes within QTL intervals that show evidence of population-specific selection in the highland sample (initial outliers include insulin signaling genes). Genes identified will be functionally tested for influence on body and wing size using a newly developed transgenic approach; specific mutations will be tested in the same way. 2. Reveal cellular mechanisms underlying body size evolution. Research will test whether changes in both cell size and number may give rise to the strikingly large wings of Ethiopian D. melanogaster. Research will also confirm whether the observed enlargement of larval muscles (polynucleate cells which strongly influence adult body size) is due to increases in the number of nuclei or their ploidy. Transgenic constructs will allow the cellular influence of specific adaptive mutations to be assessed. 3. Test whether wing size evolution disrupted developmental canalization. Ethiopian inbred lines show large wings but also very high frequencies of wing vein abnormalities. The hypothesis that phenotypic evolution has destabilized a more developmentally buffered ancestral wing state will be directly tested using a mutagenesis test of genetic perturbility. Artificial selection to recapitulate wing size evolution n the lab will further probe the generality of a link between adaptation and decanalization.

描述（由申请人提供）：本研究调查了新发现的黑腹果蝇高海拔种群的遗传基础、细胞机制以及身体和翅膀尺寸进化的发育后果，果蝇代表了该物种已知最大的果蝇。这一性状提供了独特的机会，将生物学上重要的表型差异与其潜在的细胞机制以及导致这种变化的特定基因和突变联系起来。果蝇系统为研究基因水平上的适应性进化提供了一系列优势，从群体基因组数据到转基因工具。结果将增加我们对适应的多基因性和致病变异特性的了解（例如编码与调节；新突变与现有遗传变异）。这项研究整合了生物学子学科，揭示了导致表型进化的细胞水平机制（例如细胞增殖和体细胞倍性）。它还罕见地研究了适应性进化对发育稳定性的潜在影响。这项工作将揭示进化如何改变参与胰岛素信号和细胞周期的基因功能，而不会对生物体产生有害后果——这些发现最终可能与癌症、糖尿病和其他医疗状况的研究相关。 1. 对在体型进化中发挥作用的基因进行全基因组搜索。确认它们的影响并使用转基因测试致病突变。一种新的 QTL 作图方法将致病基因定位到约 100kb 的范围内。一项新的群体遗传统计数据将揭示 QTL 区间内的基因，这些基因显示了高原样本中群体特异性选择的证据（最初的异常值包括胰岛素信号基因）。将使用新开发的转基因方法对确定的基因进行功能测试，以了解其对身体和翅膀尺寸的影响；特定突变将以同样的方式进行测试。 2. 揭示身体尺寸进化的细胞机制。研究将测试细胞大小和数量的变化是否可能导致埃塞俄比亚果蝇拥有惊人的大翅膀。研究还将确认观察到的幼虫肌肉（强烈影响成虫体型的多核细胞）的增大是否是由于细胞核数量或其倍性的增加所致。转基因构建体将允许细胞影响待评估的特定适应性突变。 3. 测试翅膀尺寸的演变是否扰乱了发育通道化。埃塞俄比亚近交系显示出较大的翅膀，但翼脉异常的频率也非常高。表型进化破坏了发育上更加缓冲的祖先翅膀状态的假设将使用遗传扰动的诱变测试直接进行测试。在实验室中进行的人工选择来概括翅膀尺寸的演变将进一步探讨适应和去通道之间联系的普遍性。