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

项目摘要 真核生物基因组含有各种进化上的“自私”遗传元件（SGE）， 以牺牲宿主为代价来传播病毒SGE分为两大类：那些扭曲公平的 孟德尔式传播（例如，减数分裂驱动元件）和相对于宿主过度复制的那些 基因组（例如，转座因子或TE）。TE特别成功，例如， 约20%的果蝇（Drosophila melanogaster）基因组、约45%的人类基因组和约85%的 玉米基因组它们在宿主中的存在和活性是导致有害突变、基因组突变和基因组突变的主要原因。 不稳定和不育。作为回应，真核生物进化出了精细的监视和抑制 检测和减轻有害影响的机制，分别。由此产生的冲突 TE和它们的宿主之间加强了分子进化的军备竞赛， 遗传分化和物种形成-新物种起源的过程。因此了解 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 基因组生物学的目标。在这里，我们建议调查两个研究得很好的分子共同进化 逆转录转座因子R1和R2与两种密切相关的果蝇宿主物种Drosophila simulans 和D.毛里求斯。这些果蝇物种是生殖隔离的多重遗传不相容性 导致其杂交后代不育或致死。我们发现这些基因中的一种 不相容性涉及体细胞组织中R1和R2反转录转座子的异常去阻遏， 一种表型缺陷综合征-包括致死性、卵至成虫发育时间延迟，以及 破坏形态发育-核糖体功能受损的特征。重要的是，R1 而R2位点特异性地插入，并因此破坏了线性排列的可感知的比例， 多拷贝核糖体基因虽然R1和R2通常在表观遗传学上是沉默的，但我们的初步发现 表明杂交基因型不能抑制R1和R2（但不能抑制其他TE），导致 插入的无功能核糖体RNA。因此，我们已经确定了物种特异性调节， 两个特征明确的TE位于特征明确的基因组位点，即核糖体RNA基因 阵我们的研究项目的目的是联合收割机遗传学，分子生物学，细胞学，下一步- 代测序和进化基因组学方法，以确定基因，分子 机制，和参与R1和R2的共同进化的进化力量，与它们的宿主物种。我们 研究有望揭示TE如何进化以逃避宿主的监视和/或抑制，如何 宿主基因组的进化反应，以及基本的，多拷贝核糖体RNA基因是如何 表观遗传学调节以优化无TE插入基因拷贝的转录。

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.