Genetical genomics of inbreeding depression

目标、目的和结果：******近亲繁殖降低了许多植物和动物物种的适应性相关特征，但也可能是新变异的来源。为了理解近亲繁殖引起的遗传变化的本质，我们需要建立基因相互作用模式和途径的模型。然后，这些模型可以使用强大的基因组工具来回顾性地推断这些行为和相互作用。******“基因基因组学”将基因表达研究与遗传连锁分析相结合，开辟了一个全新的基因表达推断类别：近亲繁殖抑制的组成表达基因之间相互作用的数量和方向。进行基因基因组学包括控制杂交、培养植物材料以提取RNA、条形码和Illumina HiSeq测序等，然后用现有软件或我们自己的程序对基因表达进行统计数据分析。******为了研究近交抑郁症的遗传结构，我们将使用猴花（Mimulus）。该属在生活史和交配制度上有很大的差异，正在成为植物进化生物学的一个模式系统。我们重点研究了四种黄猴花：远交的M. guttutus（代表祖先的远交原型），以及基本上独立衍生的近交的M. micranthus， M. platycalyx和M. lacinatus。这些物种是可杂交的，但在交配系统和近亲繁殖相关的花性状方面存在显著差异，使它们成为定量遗传研究的理想选择。******在我们提议的研究中，我们将在四个分类群中杂交六对，然后自受精杂交个体产生用于遗传基因组分析的一代（使用下面的活动3）。我们还将(1)采用“QTL谱系图谱”来推断基因表达的变化，这些变化是沿着系统发育谱系的每个分支推断出来的；(2)在涉及黄猴花物种复杂物种的扩展比较中研究表达QTL的进化，并可能与植物物种进行比较；(3)开发、评估和使用新的统计遗传方法来推断表达网络中的因果关系。预期的结果将是发现负责近交抑郁的表达和进化的基因组机制。******重要性和益处：******近亲繁殖不仅是猴花的特征，也是大多数植物和动物物种的特征。近亲繁殖甚至被用来塑造人类的进化，小种群不仅促进了独特的适应，还促进了文化和技术的进化。在HQP培训方面，目前缺乏能够跨进化、基因组学和生物信息学领域工作的科学家。在我的持续指导下，新一代的科学家将学会将基因组学和生物信息学数据应用于生态学和进化问题。

Goals, objectives and outcomes:******Inbreeding lowers fitness-related characters in many species of plants and animals, but can also be a source of novel variation. To understand the nature of genetic changes caused by inbreeding, we need models for the mode of action and the pathways of gene interaction. These models can be then used to retrospectively infer such actions and interactions using powerful genomic tools. ******“Genetical genomics” combines gene expression studies with genetic linkage analysis, and opens up an entirely new class of inferences about gene expression: the amount and direction of interaction between the component expressed genes underlying inbreeding depression. Conducting genetical genomics involves controlled crosses, growing up plant material for RNA extraction, barcoding and Illumina HiSeq sequencing or the like, and then statistical data analysis of gene expression either with established software or our own programs. ******To study the genetic architecture of inbreeding depression, we will use monkeyflower (Mimulus species). This genus has much variation of life history and mating system, and is emerging as a model system in plant evolutionary biology. We focus on four yellow monkeyflower species: outbreeding M. guttutus (representing the ancestral outbreeding archeotype), and the largely independently derived inbreeders M. micranthus, M. platycalyx and M. lacinatus. These species are intercrossible, yet conspicuously differ for mating system and floral traits related to inbreeding, making them ideal for quantitative genetic studies. ******In our proposed research, we will cross each of six pairings among the four taxa, then self-fertilize hybrid individuals to produce the generation for genetical genomic analysis (using activity 3 below). We will also (1) employ “QTL lineage mapping” to infer changes of gene expression are inferred along each branch of a phylogenetic lineage, (2) examine expression QTL evolution in extended comparisons involving species within the yellow monkeyflower species complex, and possibly comparisons with plant species, and (3) develop, evaluate, and use a new statistical genetic approach to infer causation in expression networks. The expected outcomes will the discovery of genomic mechanisms responsible for the expression and evolution of inbreeding depression.******Importance and benefits:******Inbreeding is not just a feature of monkeyflowers, but of most plant and animal species. Inbreeding has even been invoked to shape human evolution, with small populations fostering not only unique adaptations, but also the evolution of culture and technology. With regard to training of HQP, there is currently a shortage of scientists who can work across the boundary of evolution, genomics and bioinformatics. With my continued tutorage, a new generation of scientists will learn to apply genomics and bioinformatic data to questions in ecology and evolution.