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

项目摘要 真核生物基因组中含有各种进化上的“自私”遗传元件(SGE)，它们试图确保 它们的传播是以宿主为代价的。SGE分为两大类：扭曲公平的SGE 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那些 基因组(例如，转座元件，或TES)。TES特别成功，例如制宪 ~20%的果蝇(黑腹果蝇)基因组，~45%的人类基因组，~85%的 玉米基因组。它们在宿主中的存在和活性是有害突变的主要原因，基因组 不稳定和不孕不育。作为回应，真核生物进化出了精心设计的监视和抑制 检测和减轻TES有害影响的机制。由此产生的冲突 TES和它们的宿主之间的竞争加剧了分子进化军备竞赛，这可能导致快速的种群 遗传分化和物种形成--新物种起源的过程。因此，理解 TE与宿主防御系统的相互作用的遗传学、分子生物学和进化是主要的 基因组生物学的目标。在这里，我们打算研究两个研究得很好的分子共同进化 逆转座子元件R1和R2与两种近缘果蝇寄主果蝇的关系 和毛叶石杉D.mauritiana。这些果蝇物种由于多种遗传不亲和性而被生殖性隔离。 在他们的杂交后代中造成不育或致死。我们发现这些基因中的一种 不亲和性涉及体细胞组织中R1和R2反转录转座子的异常抑制 一种表型缺陷综合征--包括致命性、卵子到成体发育时间的延迟，以及 形态发育障碍--核糖体功能受损的特征。重要的是，R1 以及R2特定地插入并且因此破坏相当大比例的线状排列的， 多拷贝核糖体基因。虽然R1和R2通常是表观遗传沉默的，但我们的初步发现 发现杂交基因不能抑制R1和R2(但不抑制其他TES)，导致表达 插入的、非功能性的核糖体RNA。因此，我们已经确定了针对物种的监管 两个特征良好的TE驻留在一个特征良好的基因组位置，即核糖体RNA基因 数组。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-- 世代测序和进化基因组学方法来确定基因、分子 R1和R2与其寄主物种共同进化的机制和进化力量。我们的 研究承诺阐明TES如何进化以逃避宿主监视和/或抑制，如何 宿主基因组随着反应而进化，以及基本的、多拷贝的核糖体RNA基因是如何 受表观遗传调控，以优化TE无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.