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能力的基础。了解生物体适应一系列环境的能力的局限性，有助于了解病原体如何对人类环境作出反应（例如，抗生素耐药性），以及人类如何在不适当的情况下对当前环境作出反应（例如，肥胖）。这项研究验证了这样一个假设，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，从而多效性，大大减少。与此同时，高度模块化的基因表达也带来了潜在的代价：当不经常经历替代环境时，对环境特异性基因的选择减弱，可能发生突变积累。这些假设将在进化发育遗传学中一个新出现的模型系统中得到检验：食蚁兽属的归巢甲虫。这些昆虫根据幼虫的营养表现出高度分化的可选表型。这种可选择的形态是通过在性状发育过程中共享的基因以及不同形态特有的基因的表达而发展起来的。这项研究通过对比有角甲虫（好斗的战士）和无角甲虫（不好斗的运动鞋）的第二性特征（角）和大脑的发育来验证几种预测。这项研究测试了物种内部和物种之间的四个预测：1)环境特异性基因表达的增加将与更大范围的可塑性进化相关；2)形态行为和形态发展的特异性基因将比形态之间共享的基因更具遗传变异性；3)形态发展的特异性基因由于弱选择而具有更高的遗传分化率；4)形态特异性基因将在形态之间的分化中发挥功能作用。这项工作将使用为食土甲虫开发的各种工具，包括通过微阵列分析转录谱，以及通过RNA干扰基因敲除来研究基因功能。的相关性。了解基因表达可塑性的进化限制对公众健康具有重要意义。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。我们可能会了解为什么人类不能在广泛的环境中表达促进健康的基因，比如诱发糖尿病的营养环境或老化的大脑的变化。

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.