Rapid evolution of pigmentation in D. melanogaster: from cis regulation to phenotype

项目摘要 快速进化适应是生物学的一个基本过程，也是人类面临的许多问题的核心 包括癌症、细菌和病毒性疾病、抗药性和杀虫剂抗药性的演变以及生物反应 to global全球change更改.许多快速进化的性状是复杂的和多基因的，我们缺乏一个全面的 了解自然种群快速进化的遗传和进化动力学。色素沉着 是由多个基因座决定的复杂表型。从胡椒蛾到口袋鼠， 着色被广泛观察，在许多情况下，一些大的影响位点已被确定，然后显示 机械地负责。黑腹果蝇的色素沉着模式也被认为是 适应性，在多个尺度上表现出倾向，但遗传结构和进化动力学是 更复杂：身体各节呈现出各种颜色和图案，数十个位点影响着 色素沉着已被证实，不同部分之间的模式并不总是高度相关的。我们 初步数据表明色素沉着在自然种群中可以非常迅速和周期性地进化， 季节性地在冬季后的深色和夏季后的浅色之间波动。上百个等位基因 频率的变化，并与色素沉着表型的快速演变。快速季节性 D.色素的进化黑腹肌不是几个大的影响位点的例子，但代表了一个 不同的范式支撑着复杂性状的快速进化。快速变革的需要与 在发育过程中，温度引起色素沉着的立即变化， 但热可塑性不能解释季节性色素沉着反应。我们观察到， 中间点以及极端分布的增加。人口中点的移动可能不是由于 与驱动极端表型的基因座相同。已知的色素沉着有20多种 由顺式调节控制并与多种转录因子相关的基因座。色素沉着变化 可能是在大量基因座中触发顺式调节的反式因子中频率转移的结果， 也可能是顺式效应的直接变化。选择的目标可能数量很少，也可能代表 一个更大的突变目标，测试并行性将使我们能够确定突变目标的大小。在这 建议我们调查色素沉着快速进化的遗传学，目的是回答以下问题 问题：负责色素沉着平均变化的基因座是否与极端表型中的基因座相同？ 快速定向选择的目标在种群中是否相同？色素沉着特征是否直接 负责快速适应？顺式调节变化是否发生在不同空间位置的同一组基因座上？ 和时间尺度为了实现这些目标，我们计划了一套全面的实验，使用 一种创新的方法和新的实验材料，将提供对遗传学的基本见解， 自然种群的快速进化。

PROJECT SUMMARY Rapid evolutionary adaptation is a foundational process in biology and at the core of many issues facing humanity including cancer, bacterial and viral diseases, evolution of drug and pesticide resistance, and biological response to global change. Many traits that evolve rapidly are complex and polygenic, and we lack a comprehensive understanding of the genetic and evolutionary dynamics of rapid evolution in natural populations. Pigmentation is a complex phenotype determined by many loci. From the peppered moth to the pocket mouse, adaptive coloration is widely observed and, in many cases, a few large effect loci have been identified and then shown mechanistically to be responsible. Patterns of pigmentation in Drosophila melanogaster are also thought to be adaptive, exhibiting clines at multiple scales, yet the genetic architecture and evolutionary dynamics are substantially more complex: body segments exhibit a variety of colors and patterns, dozens of loci affecting pigmentation have been verified, and patterns among different segments are not always highly correlated. Our preliminary data demonstrate that pigmentation can evolve very rapidly and cyclically in natural populations, fluctuating seasonally between dark coloration post-winter and light coloration post-summer. Hundreds of alleles change in frequency and are associated with the rapid evolution of pigmentation phenotype. Rapid seasonal evolution of pigmentation in D. melanogaster is not an example of a few loci of large effect, but represents a different paradigm underpinning the rapid evolution of complex traits. The need for rapid change is associated with a plastic response in which temperature causes an immediate change in pigmentation during development, but thermal plasticity does not explain the seasonal pigmentation response. We observe both durable shifts in midpoints as well as an increase in the distribution of the extremes. Shifts in population midpoint may not be due to the same set of loci as those that drive the phenotypic extremes. There are more than 20 known pigmentation loci controlled by cis regulation and associated with a diverse set of transcription factors. Pigmentation changes could be a result of shifting frequencies in trans factors that trigger cis regulation among a large number of loci, or it could be changes in cis effects directly. The targets of selection may be small in number or may represent a larger mutational target, and testing parallelism will enable us to determine the mutational target size. In this proposal we survey the genetics of rapid evolution in pigmentation with the goal of answering the following questions: Are the loci responsible for the average shift in pigmentation the same as loci in phenotypic extremes? Are the targets of rapid directional selection the same among populations? Are pigmentation traits directly responsible for rapid adaptation? Are cis regulatory changes occurring in the same set of loci at different spatial and temporal scales? To accomplish these goals we have planned a comprehensive set of experiments, using an innovative approach and novel experimental material, that will provide fundamental insight into the genetics of rapid evolution in natural populations.