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 基本的染色体生物学，如染色体分离和基因组完整性的保存， 在生命之树中保存下来。巧合的是，许多支持这些染色体功能的蛋白质， 未保守的结构域和残基甚至在密切相关的物种之间迅速进化。一项重要决议 对于这一悖论，他假设，必需的染色体蛋白质迅速进化，以跟上染色体蛋白质的进化速度。 富含串联重复DNA序列的区域易于阵列大小频繁变化， 在短时间的进化过程中，这种重复DNA的周转危及染色体 功能，触发染色体蛋白质的适应性进化以恢复这些功能。这个概念 基因组内协同进化的模型是在二十年前提出的，然而DNA重复，染色体重复， 蛋白质，以及由基因组内共同进化塑造的重要染色体生物学在很大程度上是未知的。 为了实验性地测试这个模型，我在基因组中的当代DNA重复序列之间产生了一个“进化失配”。 黑腹果蝇及其近缘姐妹种果蝇的快速进化染色体蛋白质。 simulans。为了产生这些错配，我利用CRISPR/Cas9介导的编辑来交换天然的 D.染色体蛋白melanogaster与D. simulans。通过这种方式，我 最近的工作表明，特别是在D.卵巢富集的simulans等位基因 染色体蛋白、MH和D.黑素胃特异性359 bp重复序列。我的发现显示， DNA：蛋白质协同进化是保持女性生殖细胞基因组完整性所必需的。该系统目前 独特地准备揭示染色体生物学和共同进化所塑造的进化后果。 在这里，我整合进化，细胞生物学和生物化学的方法来研究染色体生物学 保留359 bp：MH协同进化。我还探讨了359 bp：MH共同进化如何在生物学中产生影响。 DNA：蛋白质界面，引发可能导致物种间杂交的次级共同进化过程 不相容性最后，我探讨了进化创新在全球的普遍性和后果。 果蝇遗传学中的动态MH基因家族。