Molecular and evolutionary genetics of retrotransposon-mediated interspecific hybrid incompatibility in Drosophila

果蝇逆转录转座子介导的种间杂种不相容性的分子和进化遗传学

基本信息

批准号：
10312106
负责人：
DAVEN C PRESGRAVES
金额：
$ 30.8万
依托单位：
UNIVERSITY OF ROCHESTER
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-01-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10312106
关键词：
Adult Biology Candidate Disease Gene Characteristics Chromatin Circular DNA Conflict (Psychology)Cytology DNA Insertion Elements DNA Transposable Elements Data Defect Development Drosophila genus Drosophila melanogaster Elements Ensure Epigenetic Process Etiology Eukaryota Evolution Floods Gene Dosage Genes Genetic Genetic Drift Genetic Transcription Genetic Transformation Genome Genomic Instability Genomics Genotype Goals Heterochromatin Host Defense Human Human Genome Hybrids Infertility Larva Light Link Maize Maps Mediating Meiosis Methods Molecular Molecular Biology Morphology Mutation Organism Paste substance Phenotype Population Genetics Process Recording of previous events Regulation Reporter Repression Reproduction Research Research Project Grants Retrotransposon Ribosomal DNA Ribosomal RNA Ribosomes Role Running Selfish Genes Siblings Sister Site Small Interfering RNA Source Species Specificity Sterility Structure Syndrome System Testing Time Tissues Transcript Transgenes Work X Chromosome arms race egg epigenetic regulation epigenetic silencing experience falls fly genetic evolution genomic locus insight next generation sequencing novel overexpression rRNA Genes reproductive response segregation success transmission process

项目摘要

Project Summary Eukaryotic genomes harbor a variety of evolutionarily “selfish” genetic elements (SGEs) that seek to ensure their transmission at the expense of their hosts. SGEs fall into two broad classes: those that distort fair Mendelian transmission (e.g., meiotic drive elements) and those that over-replicate relative to the host genome (e.g., transposable elements, or TEs). TEs have been especially successful, e.g. constituting ~20% of the fruitfly (Drosophila melanogaster) genome, ~45% of the human genome, and ~85% of the maize genome. Their presence and activity in hosts are major causes of deleterious mutation, genome instability, and infertility. Eukaryotes have, in response, evolved elaborate surveillance and suppression mechanisms to detect and mitigate the deleterious effects of TEs, respectively. The resulting conflicts between TEs and their hosts potentiate molecular evolutionary arms races that can cause rapid population genetic divergence and speciation— the process by which new species originate. Therefore, understanding the genetics, molecular biology, and evolution of TE interactions with the host defense apparatus are major goals of genome biology. Here we propose to investigate the molecular coevolution of two well-studied retrotransposable elements, R1 and R2, with two closely related fruitfly host species, Drosophila simulans and D. mauritiana. These fruitfly species are reproductively isolated by multiple genetic incompatibilities that cause sterility or lethality in their hybrid progeny. We have discovered that one of these genetic incompatibilities involves the aberrant de-repression of R1 and R2 retrotransposons in somatic tissues and a syndrome of phenotypic defects— including lethality, delayed egg-to-adult development time, and disrupted morphological development— characteristic of compromised ribosomal function. Importantly, R1 and R2 insert site-specifically into, and thus disrupt, an appreciable proportion of the linearly arrayed, multicopy ribosomal genes. While R1 and R2 are normally epigenetically silenced, our preliminary findings reveal that hybrid genotypes fail to suppress R1 and R2 (but not other TEs), resulting in the expression of inserted, non-functional ribosomal RNAs. We have therefore identified the species-specific regulation of two well-characterized TEs that reside in a well-characterized genomic locus, the ribosomal RNA gene array. The aims of our research project are to combine genetics, molecular biology, cytology, next- generation sequencing, and evolutionary genomics methods to determine the genes, molecular mechanisms, and evolutionary forces involved in the coevolution of R1 and R2, with their host species. Our research promises to shed light on how TEs evolve to evade host surveillance and/or suppression, how hosts genomes evolve in response, and how the essential, multicopy ribosomal RNA genes are epigenetically regulated to optimize transcription of TE insertion-free gene copies.

项目概要真核基因组包含各种进化上的“自私”遗传元件（SGE），旨在确保它们以牺牲主机为代价的传输分为两大类：扭曲公平的传输。孟德尔传递（例如减数分裂驱动元件）和相对于宿主过度复制的传递基因组（例如转座元件或 TE）尤其成功，例如约 20% 的果蝇（果蝇）基因组、约 45% 的人类基因组和约 85% 的基因组它们在宿主中的存在和活性是基因组有害突变的主要原因。作为回应，真核生物进化出了复杂的监视和抑制。分别检测和减轻 TE 有害影响的机制。 TE 与其宿主之间的分子进化军备竞赛会加剧，从而导致快速繁殖遗传分化和物种形成——新物种起源的过程因此需要理解。 TE 与宿主防御装置相互作用的遗传学、分子生物学和进化是主要的在这里，我们建议研究两个经过充分研究的分子共同进化。逆转录转座元件 R1 和 R2 与两种密切相关的果蝇宿主物种——果蝇这些果蝇物种因多种遗传不相容性而被生殖隔离。导致其杂交后代不育或致死的原因之一是我们发现了其中的遗传因素。不相容性涉及体细胞组织中 R1 和 R2 逆转录转座子的异常去抑制表型缺陷综合征——包括致死性、卵子到成虫发育时间延迟，以及形态发育受损——核糖体功能受损的特征。重要的是，R1。 R2 位点特异性插入，从而破坏线性排列的相当一部分，虽然 R1 和 R2 通常是表观遗传沉默的，但我们的初步发现揭示杂交基因型无法抑制 R1 和 R2（但不能抑制其他 TE），导致表达因此，我们确定了插入的非功能性核糖体 RNA 的物种特异性调控。两个已充分表征的 TE，它们位于已充分表征的基因组位点（核糖体 RNA 基因）中我们研究项目的目标是将遗传学、分子生物学、细胞学、下一步结合起来。世代测序和进化基因组学方法来确定基因、分子 R1 和 R2 与其宿主物种共同进化所涉及的机制和进化力量。对承诺的研究揭示了 TE 如何进化以逃避宿主监视和/或压制，如何宿主基因组响应而进化，以及重要的多拷贝核糖体 RNA 基因是如何发挥作用的表观遗传调控可优化 TE 无插入基因拷贝的转录。