Modularity of gene expression and tradeoffs in the evolution of plasticity

描述(由申请人提供)：基因表达的可塑性是生物体应对环境变化的大部分能力的基础。了解生物体适应一系列环境的能力限制，对于理解病原体如何对人类环境做出反应(例如，抗生素耐药性)，以及人类如何对当前环境(例如，肥胖症)做出有时不适当的反应，具有重要意义。这项研究测试了这样一种假设，即基因表达的模块化程度或环境特异性对定义可塑性进化中的极限具有基本意义。高度模块化的基因表达被认为允许适应特定的环境，因为基因功能的重叠因此多效性大大减少。与此同时，高度模块化的基因表达也有潜在的代价：当不经常经历替代环境时，对环境特定基因的选择会减弱，可能会发生突变积累。这些假说将在进化发育遗传学中一个新出现的模式系统中得到验证：食线虫属的寄居甲虫。这些昆虫根据幼虫的营养表现出高度不同的替代表型。这种可供选择的形态是通过表达在性状发育过程中共有的基因，以及不同形态特有的基因来发展的。这项研究通过对比有角甲虫(攻击性斗士)和无角甲虫(非攻击性运动鞋)甲虫的第二性征(角)和大脑的发展来测试几个预测。这项研究测试了种内和种间的四种预测：1)环境特异性基因表达的增加将与更大范围的可塑性的进化相关；2)与变形行为和形态的发展特定的基因将比那些在不同形态之间共享的基因更具遗传变异性；3)由于弱选择的结果，与形态发育相关的基因经历更高的遗传分歧率；以及4)形态特异性基因将在产生形态之间的差异中发挥作用。这项工作将使用为食线虫开发的各种工具，包括通过微阵列分析的转录图谱，以及通过RNA干扰基因敲除来研究基因功能。关联性。了解基因表达可塑性的进化极限对公共健康具有重要意义。如果我们能够抑制病原体应对多种环境的能力，例如入侵人体或处理多种药物，我们可能能够降低病原体的毒力。我们可能会了解到，为什么人类不能在广泛的环境中表达促进健康的基因，例如引发糖尿病的营养环境或老化大脑的变化。

DESCRIPTION (provided by applicant): Plasticity in gene expression underlies much of the ability of organisms to cope with environmental variation. Understanding limits in the ability of organisms to adjust to a range of environments has implications for understanding how pathogens respond to human environments (e.g., antibiotic resistance), and how humans respond, at times inappropriately, to current environments (e.g., obesity). This research tests the hypothesis that the degree of modularity, or environmental specificity, of gene expression has fundamental implications for defining limits in the evolution of plasticity. Highly modular gene expression is assumed to permit adaptation to specific environments because overlap in gene function, and thus pleiotropy, is much reduced. At the same time, highly modular gene expression comes at a potential cost: when alternative environments are experienced infrequently, selection on environment-specific genes is weakened and mutation accumulation can occur. These hypotheses will be tested in a newly emerging model system in evolutionary developmental genetics: homed beetles in the genus Onthophagus. These insects display highly divergent alternative phenotypes depending on larval nutrition. Such alternative morphs develop through expression of genes shared across the development of traits, as well as genes specific to different morphs. This research tests several predictions by contrasting the development of secondary sexual traits (horns) and brains in horned (aggressive fighter) and hornless (non-aggressive sneaker) beetle morphs. This research tests four predictions both within and between species: 1) increased environmentally-specific gene expression will be correlated with the evolution of greater ranges of plasticity, 2) genes specific to the development of morph behavior and morphology will be more genetically variable than those shared between morphs, 3) genes specific to morph development experience higher rates of genetic divergence as a result of weak selection, and 4) morph-specific genes will play functional roles in generating divergence between morphs. This work will use a variety of tools developed for Onthophagus beetles, including transcriptional profiling via microarray analysis, and investigating gene function through RNA interference gene knock-down. Relevance. Understanding evolutionary limits of plasticity in gene expression has implications for public health. If we can curb the ability of pathogens to cope with multiple environments, such as invading the human body or dealing with multiple medications, we may be able to reduce pathogen virulence. We may learn why humans cannot express genes that promote health in a wide range of environments, such as diabetes-inducing nutritional environments or changes in the aging brain.