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 杂交功能障碍提供了一个无与伦比的窗口，以进化驱动因素和遗传基础的分歧，在关键 发展过程。杂交功能障碍也会导致生殖隔离，并有助于物种形成。内- 基因组冲突可能在这种分化中起核心作用，并成为杂种功能障碍的基础，但经验性测试很少。 在胎生生物中，一个常见的冲突来源是母畜和雄畜在资源分配上的冲突 发展后代（例如父母冲突）。父母冲突可能会推动基因组印记的进化; 表观遗传现象，即等位基因具有来源特异性表达的亲本。在父母冲突下， 印迹基因的缺失导致胎座或胚乳发育异常，随后导致杂种胚死亡。这个早期 在哺乳动物和植物的杂种中，开始的不活泼是常见的，但是潜在的基因是未知的。我将向 通过配对人口和定量基因组学，基因表达和功能遗传学来识别 杂种种子不活力的遗传基础，并测试亲本冲突在产生这种障碍中的作用。 我最近在遗传学和进化的最广泛研究模型之一--米姆卢斯--中发现了一个物种 点滴状种复合体尽管最近分裂（~ 230 KYA），M。decorus和M.点滴虫通过生殖隔离， 由胚乳发育不典型引起的杂种种子的无活力。杂交种子的无活力性迅速而反复地 在这个群体中进化，至少有两个独立的发病率在~ 230 KYA。生殖方面的这种异常多样性 隔离，再加上M. Guttatus使其成为研究 杂种种子无活力的遗传基础。通过量化物种间的表达差异，我将描述 印迹的表观基因组景观和评估，如果印迹分歧是由自然选择驱动。我会一前一后 绘制杂交种子多个无活力发生的遗传基础图，以评估无活力基因座的重叠程度， 估计冲突驱动的进化的可重复性。然后，我将确定候选基因，并通过以下方法对其进行功能测试： 构建改变印迹基因表达的转基因系，并定量异常印迹表达是否导致 不能生存;父母冲突的主要预测。最后，使用复制的接触区，我将评估 这些物种之间的渐渗，以估计杂交种子的无效性作为基因流的障碍的功效。通过使用 祖先不平衡的模式，我还可以识别其他假定的不相容等位基因。因为我已经生成了一组 从这些接触区的不朽的近交系，我可以复活特定的基因型，进行操纵杂交， 鉴定推定的不亲和表型，从而将长期选择模式与特定的杂交表型连接起来。 这个项目将导致一个共同的和重要的生殖障碍的整体遗传解剖;从其 分子遗传学基础来量化这些等位基因在限制自然界基因渗入中的作用。鉴于许多人 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 表达变异对人类健康也有重要意义。

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