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.

项目摘要 混合功能障碍为钥匙中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。混合功能障碍还可以赋予生殖隔离并有助于物种形成。内 基因组冲突可能在这种分歧中起着核心作用，并且是混合功能障碍的基础，但经验测试很少。 胎生生物中的冲突的常见来源源于大坝和乳房之间的冲突，以分配资源 发展后代（例如父母冲突）。父母的冲突可能会推动基因组烙印的演变；一个 表观遗传现象，等位基因具有特定于原始的父母的表达。在父母的冲突下 烙印基因会导致异常的胎盘或胚乳发育，并随后杂交胚胎死亡。这个早 在哺乳动物和植物杂种中，发作的不可分割性都是常见的，但是潜在的基因尚不清楚。我会解决的 通过配对种群和定量基因组学，基因表达和功能遗传学来鉴定这些知识差距 混合种子不可分割性的遗传基础并测试父母冲突在产生这一障碍中的作用。 我最近在研究最广泛的遗传学模型和进化模型之一中发现了一个物种 - 模拟物 Guttatus物种复合物。尽管最近进行了分裂（〜230kya），但M. Decorus和M. Guttatus还是通过生殖隔离 由非典型胚乳发育引起的杂交种子不可分割性。混合种子的不可分割性迅速而反复 在这一组中进化，在〜230Kya中至少有两个独立的事件。这种生殖的杰出多样性 隔离，与Guttatus巨大的遗传和基因组资源相吻合，使其成为研究的理想系统 混合种子不可分割的遗传基础。通过量化物种之间的表达差异，我将表征 印迹的表观基因组景观，并评估印迹中的差异是否由自然选择驱动。在同时，我会 绘制杂交种子不可分割性多个发生率的遗传基础，以评估不可侵袭性基因座重叠的程度 估计冲突驱动的进化是多么可重复。然后，我将识别候选基因并通过功能来测试 构建转基因线，以改变印迹基因表达并量化异常印迹表达原因 入侵性；父母冲突的中心预测。最后，使用复制的接触区，我将评估 这些物种之间的渗入以估计杂交种子不可分割性作为基因流动的障碍的功效。通过使用 祖先不平衡的模式，我还可以识别其他推定的不相容性等位基因。当我生成一组 这些接触区的不朽近交系，然后我可以复活特定的基因型，执行操纵杂交，然后 识别推定的不兼容表型，从而与特定的混合表型一起弥合了长期选择模式。 该项目将导致对常见和重要的生殖屏障的整体遗传解剖；从它的 分子遗传基础，以量化这些等位基因在限制自然界中的渗入中的作用。鉴于许多人 疾病是由印迹基因的征服产生的，理解了塑造印记基因的进化力 表达变异对人类健康也具有重要意义。

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