The Evolution of Genomic Imprinting and Strong Reproductive Isolation

基因组印记的演变和强生殖隔离

• 批准号: 10711685
• 负责人: Jennifer M. Coughlan
• 金额: $ 41.88万
• 依托单位: YALE UNIVERSITY
• 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 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10711685
• 关键词: Alleles; Candidate Disease Gene; Chromosome Mapping; Complex; Conflict (Psychology); Development; Developmental Process; Dissection; Embryo; Embryo Deaths; Epigenetic Process; Evolution; Functional disorder; Gene Expression; Genes; Genetic; Genetic Models; Genetic study; Genome; Genomic Imprinting; Genomics; Genotype; Health; Human; Hybrids; Inbreeding; Incidence; Knowledge; Mimulus; Molecular Genetics; Natural Selections; Nature; Organism; Parents; Pattern; Phenotype; Placenta; Plants; Play; Population; Process; Resource Allocation; Role; Shapes; Source; Study models; System; Techniques; Testing; Tissues; Transgenic Organisms; Work; candidate identification; early onset; epigenomics; gene expression variation; genetic approach; genetic resource; genome resource; human disease; imprint; offspring; parental role; reproductive; stem

Project Summary Hybrid dysfunction offers an unparalleled window into the evolutionary drivers and genetic basis of divergence in key developmental processes. Hybrid dysfunction can also confer reproductive isolation and contribute to speciation. Intra- genomic conflicts may play a central role in this divergence, and underlie hybrid dysfunction, but empirical tests are few. A common source of conflict in viviparous organisms stems from conflict between dams and sires for resource allocation to developing offspring (e.g. parental conflict). Parental conflict may drive the evolution of genomic imprinting; an epigenetic phenomenon whereby alleles have parent-of-origin-specific expression. Under parental conflict, misregulation of imprinted genes causes abnormal placenta or endosperm development, and subsequently hybrid embryo death. This early onset inviability is common in both mammalian and plant hybrids, but the underlying genes are unknown. I will address this knowledge gap by pairing population and quantitative genomics, gene expression, and functional genetics to identify the genetic basis of hybrid seed inviability and test the role of parental conflict in generating this barrier. I recently discovered a species in one of the most widely studied models for genetics and evolution- the Mimulus guttatus species complex. Despite a recent split (~230KYA), M. decorus and M. guttatus are reproductively isolated via hybrid seed inviability caused by atypical endosperm development. Hybrid seed inviability has rapidly and repeatedly evolved in this group, with at least two independent incidences in ~230KYA. This exceptional diversity in reproductive isolation, paired with the tremendous genetic and genomic resources of M. guttatus makes it an ideal system to study the genetic basis of hybrid seed inviability. By quantifying expression differences among species, I will characterize the epigenomic landscape of imprinting and assess if divergence in imprinting is driven by natural selection. In tandem, I will map the genetic basis of multiple incidences of hybrid seed inviability to assess the extent of overlap in inviability loci and estimate how repeatable conflict-driven evolution is. I will then identify candidate genes and functionally test them by constructing transgenic lines that alter imprinted gene expression and quantify if abnormal imprinted expression causes inviability; a central prediction of parental conflict. Lastly, using replicated contact zones, I will assess the dynamics of introgression between these species to estimate the efficacy of hybrid seed inviability as a barrier to gene flow. By using patterns of ancestry disequilibrium, I can also identify other putative incompatibility alleles. As I have generated a set of immortal inbred lines from these contact zones, I can then resurrect specific genotypes, perform manipulative crosses, and identify putative incompatibility phenotypes, thus bridging long term patterns of selection with specific hybrid phenotypes. This project will result in a holistic genetic dissection of a common and important reproductive barrier; from its molecular genetic basis to quantifying the role of these alleles in limiting introgression in nature. Given that many human diseases result from misexpression of imprinted genes, understanding the evolutionary forces that shape imprinted gene expression variation also has significant implications for human health.

项目概要 混合功能障碍为了解关键差异的进化驱动因素和遗传基础提供了一个无与伦比的窗口 发展过程。杂种功能障碍还可以导致生殖隔离并促进物种形成。内部- 基因组冲突可能在这种分歧中发挥着核心作用，并且是杂交功能障碍的基础，但实证测试很少。 胎生生物冲突的一个常见根源是母体和父体之间关于资源分配的冲突 对发育中的后代（例如父母冲突）。父母冲突可能会推动基因组印记的进化；一个 等位基因具有亲本特异性表达的表观遗传现象。父母冲突、监管不当 印记基因的缺失会导致胎盘或胚乳发育异常，并随后导致杂交胚胎死亡。这早 在哺乳动物和植物杂交中，起始不存活现象很常见，但潜在的基因尚不清楚。我将解决 通过将群体与定量基因组学、基因表达和功能遗传学配对来识别这一知识差距 杂交种子不存活的遗传基础并测试亲本冲突在产生这种障碍中的作用。 我最近在最广泛研究的遗传学和进化模型之一中发现了一个物种——酸酸浆 guttatus 物种复合体。尽管最近发生了分裂（~230KYA），M. decus 和 M. guttatus 通过以下途径进行生殖隔离： 非典型胚乳发育导致杂种种子无法存活。杂交种子的不活力已迅速且反复发生 在该群体中进化，在~230KYA 中至少有两次独立的发生率。这种非凡的生殖多样性 分离，加上 M. guttatus 巨大的遗传和基因组资源，使其成为研究 杂交种子不活力的遗传基础。通过量化物种之间的表达差异，我将描述 印记的表观基因组景观并评估印记的分歧是否是由自然选择驱动的。同时，我将 绘制杂交种子不活力的多种发生率的遗传基础，以评估不活力基因座的重叠程度，并 估计冲突驱动进化的可重复性。然后我将识别候选基因并通过以下方式对其进行功能测试 构建改变印记基因表达的转基因系，并量化异常印记表达是否导致 不可生存性；父母冲突的核心预测。最后，使用复制的接触区，我将评估 这些物种之间的基因渗入，以评估杂交种子的不活力作为基因流动障碍的功效。通过使用 通过祖先不平衡的模式，我还可以识别其他假定的不相容等位基因。因为我已经生成了一组 来自这些接触区的不朽的近交系，然后我可以复活特定的基因型，进行操纵杂交，并且 识别假定的不相容表型，从而将长期选择模式与特定的杂交表型联系起来。 该项目将对常见且重要的生殖障碍进行全面的基因剖析；从它的 量化这些等位基因在限制自然界渗入中的作用的分子遗传学基础。鉴于许多人类 疾病是由印记基因的错误表达引起的，了解塑造印记基因的进化力量 表达变异也对人类健康具有重大影响。

项目成果

The role of conflict in shaping plant biodiversity.

冲突在塑造植物生物多样性中的作用。

• DOI: 10.1111/nph.19233
• 发表时间: 2023
• 期刊: The New phytologist
• 作者: Coughlan,JennM