The Evolution of DNA Replication Timing in Great Apes

类人猿 DNA 复制时间的演变

• 批准号: 2415012
• 负责人: Amnon Koren
• 金额: $ 105.32万
• 依托单位: Roswell Park Cancer Institute, Division of Health Research, Inc
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-01-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2415012&HistoricalAwards=false
• 关键词: Evolution; DNA; Replication; Timing; Great

The evolution of DNA replication timing in great apesAlthough humans and our closest primate relatives (e.g., chimpanzees) are ~99% identical at the genetic level, there are clearly many differing traits, such as cognitive abilities, language, upright posture, and many more. This project will explore one genetic mechanism that could help explain those differences: the variation in the timing of DNA replication. This project will measure the progression of DNA replication across the chromosomes of many humans, chimpanzees, and other great apes. Subsequently, the project will identify differences, reconstruct their evolutionary trajectory, and link DNA replication variation to mutation rates, gene expression and possibly, the evolution of new traits. As part of the societal impact of the project, results will be disseminated to current and prospective veteran undergraduate students, a group which is under-represented in leading universities. Veterans have a high interest in STEM fields but often do not have the same opportunities to engage in biological research. The research will additionally involve undergraduate and graduate students and will develop an accessible platform for visualization of the computational data generated in this project, which will be widely shared with researchers and the public. DNA is replicated according to a defined temporal order referred to as the DNA replication timing program. DNA replication timing interfaces with gene regulation and influences mutation rates and patterns. As a result, it holds the potential of affecting evolution in non-trivial ways. On the other hand, we know very little about how DNA replication timing has itself evolved. This project will measure DNA replication timing across the genomes of ~100 humans and chimpanzees as well as other great apes, using whole-genome DNA sequencing. The generated replication timing data will be used to identify variations, infer their evolutionary patterns and genetic basis, and link them to human-specific molecular and phenotypic traits. Genes that are known to have evolved since human-chimpanzee divergence will be specifically studied for replication timing variations, and other candidate genes identified based on replication timing divergence patterns. Reciprocally, patterns of replication timing variation among great apes will be used to infer the dynamics of replication timing evolution, including the birth and death of DNA replication origins, and changes in DNA replication timing.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

类人猿 DNA 复制时间的进化虽然人类和我们最亲近的灵长类亲戚（例如黑猩猩）在基因水平上大约有 99% 相同，但显然存在许多不同的特征，例如认知能力、语言、直立姿势等等。该项目将探索一种可以帮助解释这些差异的遗传机制：DNA 复制时间的变化。该项目将测量许多人类、黑猩猩和其他类人猿染色体上 DNA 复制的进程。 随后，该项目将识别差异，重建其进化轨迹，并将 DNA 复制变异与突变率、基因表达以及可能的新性状的进化联系起来。作为该项目社会影​​响的一部分，研究结果将传播给当前和未来的退伍军人本科生，这一群体在顶尖大学中代表性不足。退伍军人对 STEM 领域有着浓厚的兴趣，但往往没有同样的机会从事生物学研究。该研究还将涉及本科生和研究生，并将开发一个可访问的平台，用于可视化该项目中生成的计算数据，该平台将与研究人员和公众广泛共享。 DNA 按照定义的时间顺序（称为 DNA 复制计时程序）进行复制。 DNA 复制时间与基因调控相互作用并影响突变率和模式。因此，它有可能以非平凡的方式影响进化。另一方面，我们对 DNA 复制时间本身是如何进化的知之甚少。该项目将使用全基因组 DNA 测序来测量约 100 只人类、黑猩猩以及其他类人猿的基因组中的 DNA 复制时间。生成的复制计时数据将用于识别变异，推断其进化模式和遗传基础，并将其与人类特有的分子和表型特征联系起来。将专门研究自人类与黑猩猩分歧以来进化的基因的复制时间变异，并根据复制时间分歧模式识别其他候选基因。反过来，类人猿之间的复制时间变异模式将被用来推断复制时间进化的动态，包括DNA复制起点的诞生和死亡，以及DNA复制时间的变化。该奖项反映了NSF的法定使命，并被认为是值得的通过使用基金会的智力优势和更广泛的影响审查标准进行评估来获得支持。