Evolutionary inference with interlocus gene conversion

位点间基因转换的进化推理

• 批准号: 1754142
• 负责人: Jeffrey Thorne
• 金额: $ 56.43万
• 依托单位: North Carolina State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1754142&HistoricalAwards=false
• 关键词: Evolutionary; inference; interlocus; gene; conversion

In humans and many other species, a majority of the genome consists of repeated DNA sequences that arose via duplications. A genetic duplication can occur when an offspring inherits two copies of a DNA sequence from a parent who only has one copy; these duplicated regions in the genome are called repeats. Following duplication events, these repeats can subsequently diverge due to mutations that affect one repeat but not others. However, this divergence can be partially or completely counteracted by a phenomenon known as interlocus gene conversion (IGC). IGC increases the similarity of repeated sequences by copying sequence stretches from one repeat copy into the corresponding region of another. The role of IGC mutations in shaping how repeated genomic regions evolve through time is poorly understood. This project aims to develop statistical methods for quantifying and incorporating the impact that IGC has in shaping genomes. By doing so, this research will illuminate the forces that shape repeated regions in genomes and will assist in understanding the biological function of these regions. Project goals will be accomplished with the assistance of undergraduate researchers. These students will have the opportunity to visit collaborators at the University of Tokyo in a cross-cultural exchange. In addition, visualizations will be created to simultaneously teach the general public about statistical inference and the forces that shape genomes.A variety of likelihood-based statistical tools for studying IGC will be developed and assessed. One goal is to learn how IGC varies among biological species and among genes. A focus will be on how IGC is influenced by whole genome versus tandem duplication. The research will investigate whether there are tendencies of some repeat copies to be donors and other repeat copies to be recipients during IGC events. Careful consideration will be made of how to accommodate IGC in detection of positive diversifying selection, divergence time estimation, and ancestral sequence reconstruction. The work will combine theoretical development, software implementation, and testing using a combination of simulation and empirical data.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.

在人类和许多其他物种中，大部分基因组由重复产生的重复 DNA 序列组成。当后代从只有一份 DNA 序列的父母那里继承两份 DNA 序列时，就会发生基因复制。基因组中的这些重复区域称为重复。重复事件发生后，这些重复序列可能会由于影响一个重复序列但不影响其他重复序列的突变而发生分歧。然而，这种差异可以被称为位点间基因转换（IGC）的现象部分或完全抵消。 IGC 通过将一个重复拷贝的序列片段复制到另一个重复拷贝的相应区域来增加重复序列的相似性。人们对 IGC 突变在塑造重复基因组区域随时间演化的过程中的作用知之甚少。该项目旨在开发统计方法来量化和整合 IGC 在塑造基因组方面的影响。通过这样做，这项研究将阐明塑造基因组中重复区域的力量，并将有助于理解这些区域的生物学功能。项目目标将在本科研究人员的协助下完成。这些学生将有机会在跨文化交流中拜访东京大学的合作者。此外，还将创建可视化，以同时向公众传授统计推断和塑造基因组的力量。将开发和评估用于研究 IGC 的各种基于可能性的统计工具。目标之一是了解 IGC 在生物物种和基因之间如何变化。重点是 IGC 如何受到全基因组与串联复制的影响。该研究将调查在 IGC 活动期间是否存在一些重复副本成为捐赠者而其他重复副本成为接受者的趋势。将仔细考虑如何在正多样化选择检测、分歧时间估计和祖先序列重建中适应 IGC。这项工作将结合理论开发、软件实施和使用模拟和实证数据进行测试。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Measuring Phylogenetic Information of Incomplete Sequence Data

• DOI: 10.1093/sysbio/syab073
• 发表时间: 2021-10-29
• 期刊: SYSTEMATIC BIOLOGY
• 影响因子: 6.5
• 作者: Seo, Tae-Kun;Gascuel, Olivier;Thorne, Jeffrey L.
• 通讯作者: Thorne, Jeffrey L.

Pedigree-based and phylogenetic methods support surprising patterns of mutation rate and spectrum in the gray mouse lemur

• DOI: 10.1038/s41437-021-00446-5
• 发表时间: 2021-07-16
• 期刊: HEREDITY
• 影响因子: 3.8
• 作者: Campbell, C. Ryan;Tiley, George P.;Yoder, Anne D.
• 通讯作者: Yoder, Anne D.