Genetical genomics of inbreeding depression

目的、目标和结果：近亲交配降低了许多动植物物种中与健康相关的特征，但也可能是新的变异的来源。为了理解近亲交配引起的遗传变化的本质，我们需要基因交互作用模式和途径的模型。然后，这些模型可以用来使用强大的基因组工具来追溯推断这种行为和相互作用。*“遗传基因组学”将基因表达研究与遗传连锁分析相结合，开辟了一类关于基因表达的全新推论：近亲繁殖抑制的基因表达成分之间相互作用的数量和方向。进行遗传基因组学包括受控杂交、生长用于RNA提取的植物材料、条形码和Illumina HiSeq测序等，然后使用现有的软件或我们自己的程序对基因表达进行统计数据分析。*为了研究近亲繁殖衰退的遗传结构，我们将使用猴子花(Mimulus物种)。该属的生活史和交配系统具有很大的多样性，是植物进化生物学的模式系统。我们重点研究了四个黄色猴花物种：近亲繁殖的古特图斯(代表祖先的近亲繁殖原型)，以及主要独立衍生的近交系金丝猴、花瓣金丝猴和金丝猴。这些物种可以相互杂交，但在交配系统和与近亲交配有关的花卉特征上存在明显差异，这使它们成为数量遗传学研究的理想选择。*在我们提议的研究中，我们将在四个分类群中杂交六对中的每一对，然后对杂交个体进行自交授粉，以产生用于遗传基因组分析的世代(使用下面的活动3)。我们还将(1)使用“QTL谱系图谱”来推断基因表达的变化是沿着系统发育谱系的每个分支推断的；(2)在涉及黄色猴花物种复合体内的物种的扩展比较中检查表达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学方法来推断表达网络中的因果关系。预期的结果将是发现近亲交配衰退的表达和进化的基因组机制。*重要性和益处：*近亲交配不仅是猴花的特征，也是大多数动植物物种的特征。近亲交配甚至被用来塑造人类的进化，小种群不仅培养了独特的适应能力，而且还促进了文化和技术的进化。关于HQP的培训，目前缺乏能够跨越进化、基因组学和生物信息学边界工作的科学家。在我的继续指导下，新一代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论的问题。

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.