Complex genetic interaction network rewiring and dynamics

复杂的遗传相互作用网络重新布线和动力学

• 批准号: RGPIN-2022-04674
• 负责人: Kuzmin, Elena
• 金额: $ 2.26万
• 依托单位: Concordia University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=745767
• 关键词: Complex; genetic; interaction; network; rewiring

Whole-genome duplication (WGD) events are pervasive in eukaryotes, shaping the genomes of simple single-celled organisms, such as yeast, as well as those of more complex metazoans, including humans. Most duplicated genes are eliminated after WGD because one copy accumulates deleterious mutations, leading to its loss. However, a significant proportion of duplicates persists, and factors that result in duplicate gene retention are poorly understood but critical for understanding the evolutionary forces that shape genomes. In yeast, whole genome duplication appears to have occurred approximately 100 Mya after the divergence of Kluyveromyces from Saccharomyces lineages and around the time of the emergence of angiosperms (flesh fruit plants) resulting in changes to their metabolic milieu. Quantifying the functional divergence of paralog pairs is of particular interest because of the strong selection against functional redundancy. Complex genetic interaction analysis has been effectively used to assess the functional relationship of duplicated genes. The goal of the proposed program is to develop a theoretical and practical framework to relate genotype-to-phenotype and genetic wiring to genome evolution, by studying how complex genetic interaction networks are modulated by environmental changes resulting in duplicated gene retention. First, we will quantify single and double mutant fitness of WGD duplicated on metabolic conditions. Second, we will map the conditional complex genetic interaction network of duplicated genes. Third, we will measure conditional trigenic interactions to define conditional functional redundancy and divergence of duplicated genes. This comprehensive network of conditional complex genetic interactions of duplicated genes will reveal mechanisms of duplicated gene retention in yeast, the evolution of conditional functional divergence of duplicated genes and help us to functionally annotate the yeast genome thereby providing insight into the genotype-to-phenotype relationship.

全基因组复制（WGD）事件在真核生物中普遍存在，塑造了简单单细胞生物（如酵母）以及更复杂的后生动物（包括人类）的基因组。大多数重复的基因在WGD后被消除，因为一个拷贝积累了有害的突变，导致其丢失。然而，很大一部分重复基因仍然存在，导致重复基因保留的因素知之甚少，但对于理解塑造基因组的进化力量至关重要。在酵母中，全基因组复制似乎发生在克鲁维酵母从酵母属谱系分化后约100 Mya，以及被子植物（肉果植物）出现的时间前后，导致其代谢环境发生变化。由于对功能冗余的强选择，量化parabolic对的功能分歧特别感兴趣。复杂遗传互作分析已被有效地用于评估重复基因的功能关系。该计划的目标是通过研究复杂的遗传相互作用网络如何受到环境变化的影响而导致重复的基因保留，从而建立一个理论和实践框架，将基因型到表型和遗传布线与基因组进化联系起来。首先，我们将量化在代谢条件下复制的WGD的单突变体和双突变体适应性。其次，我们将绘制复制基因的条件复杂遗传相互作用网络。第三，我们将测量条件三基因相互作用，以确定条件功能冗余和重复基因的分歧。这个全面的网络条件复杂的遗传相互作用的重复基因将揭示重复基因保留在酵母中的机制，重复基因的条件功能分歧的演变，并帮助我们功能注释酵母基因组，从而提供洞察基因型-表型关系。