Causes and consequences of intra-genomic coevolution

基因组内协同进化的原因和后果

基本信息

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
项目类别：
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

项目摘要

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.

项目概要基本的染色体生物学，例如染色体分离和基因组完整性的保存，是矛盾的是，支持这些染色体功能的蛋白质却在生命之树中保守。不保守——结构域和残基甚至在密切相关的物种之间也能快速进化。针对这一悖论，我们认为必需的染色体蛋白会迅速进化，以跟上染色体的发展步伐。富含串联重复DNA序列的区域容易频繁改变阵列大小和这种重复 DNA 的更替会危及染色体。功能，触发染色体蛋白的适应性进化以恢复这些功能。基因组内协同进化模型在二十年前就被提出，但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。为了通过实验测试这个模型，我在当代 DNA 重复序列之间生成了一个“进化不匹配” 果蝇及其密切相关的姐妹物种 D. 果蝇的快速进化染色体蛋白。为了生成这些不匹配，我利用 CRISPR/Cas9 介导的编辑来交换原生。来自黑腹果蝇的染色体蛋白与来自模拟果蝇的不同版本使用这种方法，我的。最近的工作表明，卵巢富集的 D. simulans 等位基因之间存在不相容性。染色体蛋白、MH 和黑腹果蝇特异性 359bp 重复序列我的发现表明： DNA：蛋白质共同进化是维持雌性种系基因组完整性所必需的。独特地揭示了共同进化所塑造的染色体生物学和进化后果。在这里，我整合进化、细胞生物学和生物化学方法来研究染色体生物学我还探讨了 359bp:MH 共同进化如何在 359bp:MH 共同进化之外产生影响。 DNA：蛋白质界面，触发二次共同进化过程，可能导致种间杂交最后，我探讨了进化创新的普遍性和后果。整个果蝇系统发育的动态 MH 基因家族。