The evolution of genomic imprinting

基因组印记的进化

• 批准号: 10321267
• 负责人: Jeffrey Good
• 金额: $ 28.92万
• 依托单位: UNIVERSITY OF MONTANA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10321267
• 关键词: Alleles; Atlases; Biodiversity; Biological Models; Candidate Disease Gene; Chromatin Structure; Complex; Congenital Disorders; DNA Methylation; Data; Development; Developmental Process; Disease model; Dwarfism; Dysplasia; Embryonic Development; Epigenetic Process; Evolution; Failure; Fetal Development; Gene Expression; Gene Expression Regulation; Genes; Genetic; Genetic Transcription; Genetic study; Genome; Genomic Imprinting; Genomic approach; Genotype; Goals; Growth; Growth Disorders; Hamsters; House mice; Human; Hybrids; Knowledge; Link; Mammals; Modeling; Molecular Genetics; Mus; Parents; Pathology; Pathway interactions; Phenotype; Placenta; Placentation; Play; Recurrence; Regulation; Regulator Genes; Regulatory Pathway; Research; Research Project Grants; Rodent; Rodent Model; Role; Series; Syndrome; System; Testing; Variant; X Chromosome; comparative; comparative genomics; developmental disease; epigenetic silencing; epigenomics; experimental study; fascinate; follow-up; gene regulatory network; genetic approach; genetic architecture; genome-wide; genomic data; imprint; insight; interest; mammalian genome; novel; programs; reproductive; trait; transcriptomics

Genomic imprinting is a form of epigenetic gene regulation that plays a key role in placental development. Imprinted expression is highly enriched within developmental pathways and, as a consequence, the disruption of imprinted pathways results in a range of congenital developmental disorders in humans and other mammals. Mammalian hybrids often manifest many of the same placental growth abnormalities, raising the intriguing possibility that recurrent developmental syndromes within and between species may reflect the disruption of common regulatory pathways. However, surprisingly little is known about the evolution of imprinted regulatory networks, and the contribution of disrupted genomic imprinting to the evolution of reproductive barriers between species remains unresolved. The proposed research will begin to overcome these fundamental gaps in knowledge by generating novel comparative genomic data on placental gene expression and genomic imprinting among closely related species and their reciprocal hybrids. Specific Aims 1 and 2 will use a series of hybrid rodent systems to generate an atlas of genome-wide placental transcription, DNA methylation, and chromatin structure across five species and two major lineages of rodents (house mice and dwarf hamsters). These unprecedented comparative data will allow us to resolve the basic epigenetic mechanisms controlling genomic imprinting and quantify how placental expression and imprinting has evolved over 30 million years of divergence. Specific Aim 3 will use a systems genetics approach to examine the genetic architecture of hybrid overgrowth, placental expression, and imprinting in dwarf hamsters and mice. These experiments will allow us to understand the mechanistic and genetic underpinnings of a common form of placental dysplasia and test the novel hypothesis the X chromosome plays a central role in the regulation of imprinted autosomal regulatory networks. The long-term goals of this research program are to (1) illuminate the basic epigenetic mechanisms controlling genomic imprinting, (2) provide insights into the evolutionary tempo and theoretical drivers of imprinting and other aspects of placental expression, (3) test hypotheses on the causal connection between disrupted imprinting and abnormal placental development, (4) understand the organization and evolution of imprinted expression networks, and (5) link these conceptual advances to understand the contribution of genomic imprinting to the origin of biological diversity.

基因组印记是一种表观遗传基因调控形式，在胎盘发育中起着关键作用。 发展印记表达在发育途径中高度富集，并且作为一种 因此，印记途径的破坏导致一系列先天性 人类和其他哺乳动物的发育障碍。哺乳动物的混血儿 许多相同的胎盘生长异常，提出了有趣的可能性， 物种内和物种间的发育综合征可能反映了共同的 调控途径。然而，令人惊讶的是，人们对印记基因的进化知之甚少。 调控网络，以及破坏基因组印记对进化的贡献。 物种之间的生殖障碍仍未解决。拟议的研究将开始， 通过产生新的比较基因组数据来克服这些基本的知识差距 近缘物种间胎盘基因表达和基因组印记的研究 正反杂交种具体目标1和2将使用一系列混合啮齿动物系统来产生 全基因组胎盘转录、DNA甲基化和染色质结构图谱 在五个物种和两个主要的啮齿动物谱系（家鼠和侏儒仓鼠）。这些 前所未有的比较数据将使我们能够解决基本的表观遗传机制， 控制基因组印记，并量化胎盘表达和印记如何 进化了三千多万年的分歧。具体目标3将使用系统遗传学 方法来检查杂交过度生长，胎盘表达， 在侏儒仓鼠和老鼠身上留下印记。这些实验将使我们了解 机制和遗传基础的一种常见形式的胎盘发育不良，并测试 一种新的假设，X染色体在印记常染色体的调节中起着核心作用， 监管网络。本研究计划的长期目标是（1）阐明基本的 控制基因组印记的表观遗传机制，（2）提供对进化的见解 印记和胎盘表达的其他方面的克里思和理论驱动因素，（3）测试 关于印迹破坏和胎盘异常之间因果关系的假说 发展，（4）了解印记表达网络的组织和进化， （5）将这些概念性进展联系起来，以了解基因组印记对 生物多样性的起源。

项目成果

Molecular Evolution of Ecological Specialisation: Genomic Insights from the Diversification of Murine Rodents.

• DOI: 10.1093/gbe/evab103
• 发表时间: 2021-07-06
• 期刊: Genome biology and evolution
• 影响因子: 3.3
• 作者: Roycroft E;Achmadi A;Callahan CM;Esselstyn JA;Good JM;Moussalli A;Rowe KC
• 通讯作者: Rowe KC

A natural variation-based screen in mouse cells reveals USF2 as a regulator of the DNA damage response and cellular senescence.

• DOI: 10.1093/g3journal/jkad091
• 发表时间: 2023-07-05
• 期刊: G3 (Bethesda, Md.)

Molecular Evolution across Mouse Spermatogenesis.

• DOI: 10.1093/molbev/msac023
• 发表时间: 2022-02-03
• 期刊: Molecular biology and evolution
• 影响因子: 10.7
• 作者: Kopania EEK;Larson EL;Callahan C;Keeble S;Good JM
• 通讯作者: Good JM

Automated Nuclear Cartography Reveals Conserved Sperm Chromosome Territory Localization across 2 Million Years of Mouse Evolution.

自动核制图揭示了 200 万年小鼠进化过程中保守的精子染色体区域定位。

• DOI: 10.3390/genes10020109
• 发表时间: 2019
• 期刊: Genes
• 影响因子: 3.5
• 作者: Skinner,BenjaminMatthew;Bacon,Joanne;Rathje,ClaudiaCattoni;Larson,EricaLee;Kopania,EmilyEmikoKonishi;Good,JeffreyMartin;Affara,NabeelAhmed;Ellis,PeterJamesIvor
• 通讯作者: Ellis,PeterJamesIvor

Adaptive structural and functional evolution of the placenta protects fetal growth in high-elevation deer mice.

• DOI: 10.1073/pnas.2218049120
• 发表时间: 2023-06-20
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Wilsterman, Kathryn;Moore, Emily C.;Schweizer, Rena M.;Cunningham, Kirksey;Good, Jeffrey M.;Cheviron, Zachary A.
• 通讯作者: Cheviron, Zachary A.