Causes and consequences of intra-genomic coevolution

基因组内协同进化的原因和后果

• 批准号: 10644124
• 负责人: Cara Brand
• 金额: $ 12.49万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10644124
• 关键词: Alleles; Biochemical; Biochemistry; Biological Assay; Biology; CRISPR/Cas technology; Candidate Disease Gene; Cell physiology; Cellular biology; Chromosome Segregation; Chromosome abnormality; Chromosomes; Complex; Congenital Abnormality; DNA; DNA Damage; DNA Repair; DNA Repair Pathway; DNA Sequence; DNA-protein crosslink; Development; Drosophila genus; Drosophila melanogaster; Evolution; Family member; Female; Gene Family; Genes; Genetic; Genome; Hybrids; Immunologic Factors; Internet; Interphase; Lesion; Life; Maintenance; Malignant Neoplasms; Mediating; Modeling; Oogenesis; Ovary; Peptide Hydrolases; Phylogenetic Analysis; Phylogeny; Play; Postdoctoral Fellow; Process; Proteins; Recurrence; Research; Resolution; Role; Satellite DNA; Scanning; Shapes; Side; Sister; Stretching; System; Tandem Repeat Sequences; Testing; Time; Transgenes; Trees; Untranslated RNA; Vision; Work; X Chromosome; crosslink; functional restoration; genome integrity; genome sequencing; innovation; mutant; pathogen; preservation; protein crosslink; repaired; reproductive; whole genome

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.

项目摘要 必需的染色体生物学，例如染色体分离和基因组完整性的保存是 在整个生命之树中保守。矛盾的是，许多支持这些染色体功能的蛋白质是 未经保守的 - 域并在密切相关的物种之间迅速保留进化。领先的分辨率 对于这个悖论，认为必不可少的染色体蛋白会迅速发展以与染色体保持同步 富含串联重复的DNA序列的区域容易发生阵列大小和 在短时间的进化时间内组成。重复的DNA危及染色体的营业额 功能，触发染色体蛋白的适应性演变以恢复这些功能。这个概念 二十年前提出了基因组内相结合的模型，但DNA重复序列是染色体 蛋白质和由基因组内的雕刻的重要染色体生物学在很大程度上没有表征。 为了实验测试，我在当代DNA重复之间产生了一个“进化不匹配” 果蝇Melanogaster和来自其密切相关姊妹物种的快速发展的染色体蛋白。 Simulans。为了产生这些不匹配，我利用CRISPR/CAS9介导的编辑来交换本地 来自D. melanogaster的染色体蛋白，带有来自D. simulans的发散版本。使用这种方法，我 最近的工作证明了卵巢富含的D. simulans等位基因之间的不兼容性 染色体蛋白，MH和D. melanogaster特异性359bp重复序列。我的发现表明 DNA：需要蛋白质的进化来保留雌性种系中的基因组完整性。这个系统现在是 独特的中毒，以揭示通过共同进化雕刻的染色体生物学和进化后果。 在这里，我整合了进化，细胞生物学和生物化学方法来研究染色体生物学 由359bp保留：MH协同进化。我还探究了359bp：MH的共同进化如何回荡 DNA：蛋白质界面，触发二次共同进化过程，可能导致种间杂交 不兼容。最后，我探索了进化创新的普遍性和后果 动态MH基因家族跨果蝇系统发育。