Causes and consequences of intra-genomic coevolution

项目总结 基本的染色体生物学，如染色体分离和保持基因组完整性，是 守护在生命之树上。矛盾的是，许多支持这些染色体功能的蛋白质 非保守结构域和残基甚至在亲缘关系密切的物种之间也会迅速进化。领先的决议 对这一悖论的假设是，基本的染色体蛋白质进化迅速，以跟上染色体的步伐 富含重复DNA序列的区域易于频繁改变阵列大小和 在很短的进化时间内的组成。这种重复DNA的更替危及染色体 功能，触发染色体蛋白质的适应性进化来恢复这些功能。这一概念 基因组内共同进化的模式是20年前提出的，然而DNA重复，染色体 蛋白质，以及由基因组内共同进化形成的重要的染色体生物学，在很大程度上是没有特征的。 为了实验测试这个模型，我产生了当代DNA重复序列之间的“进化不匹配”。 黑腹果蝇和其近亲种D。 人形动物。为了生成这些不匹配，我利用CRISPR/Cas9中介的编辑来交换本机 黑腹盘藻的染色体蛋白与模拟盘尾丝虫的不同版本。使用这种方法，我的 最近的研究表明，卵巢丰富的D-Simans等位基因之间存在特殊的不亲和性 染色体蛋白、MH和D黑腹果蝇特有的359bp重复序列。我的调查结果显示 DNA：蛋白质共同进化是维持雌性生殖系基因组完整性所必需的。这个系统现在是 独一无二地准备揭示共同进化塑造的染色体生物学和进化后果。 在这里，我结合进化论、细胞生物学和生物化学的方法来研究染色体生物学。 由359bp保存：MH共同进化。我还探讨了359个基点：MH共同进化是如何超越 DNA：蛋白质界面，触发二次共同进化过程，可能导致物种间杂交 不兼容。最后，我探讨了进化创新的普及性和后果 动态MH基因家族在果蝇系统发育中的应用。

PROJECT SUMMARY Essential chromosome biology such as chromosome segregation and the preservation of genome integrity are conserved across the tree of life. Paradoxically, many proteins that support these chromosome functions are unconserved—domains and residues evolve rapidly between even closely related species. A leading resolution to this paradox posits that essential, chromosomal proteins evolve rapidly to keep pace with chromosomal regions enriched with tandemly repeating DNA sequences prone to frequent changes in array size and composition across short stretches of evolutionary time. This turnover of repetitive DNA imperils chromosome functions, triggering adaptive evolution of chromosomal proteins to restore these functions. This conceptual model of intra-genomic coevolution was proposed two decades ago, and yet the DNA repeats, the chromosomal proteins, and the vital chromosome biology sculpted by intra-genomic coevolution are largely uncharacterized. To experimental test this model, I generate an “evolutionary mismatch” between contemporary DNA repeats in Drosophila melanogaster and a fast-evolving chromosomal proteins from its closely related sister species D. simulans. To generate these mismatches, I leverage CRISPR/Cas9-mediated editing to swap native chromosomal proteins from D. melanogaster with diverged versions from D. simulans. Using this approach, my recent work demonstrates an incompatibility specifically between the D. simulans allele of the ovary-enriched chromosomal protein, MH, and the D. melanogaster-specific 359bp repeats. My findings revealed that DNA:protein coevolution is required to preserve genome integrity in the female germline. This system is now uniquely poised to reveal the chromosome biology and evolutionary consequences sculpted by coevolution. Here I integrate evolutionary, cell biology, and biochemistry approaches to investigate the chromosome biology preserved by 359bp:MH coevolution. I also probe how 359bp:MH coevolution reverberates beyond the DNA:protein interface, triggering a secondary coevolutionary process that may result in an interspecies hybrid incompatibility. Finally, I explore the pervasiveness and the consequences of evolutionary innovation at the dynamic MH gene family across the Drosophila phylogeny.