IMAGiNE: Collaborative Research: Epigenetic potential and range expansion in the house sparrow

一些物种成功地殖民了地球上的大部分地区，但其他物种的地理范围很窄。回答为什么一些物种可以在如此多的地方生存对基础生物学来说是有趣的，因为它揭示了进化过程的细节。然而，这种形式的研究也有实用价值，因为它可以帮助我们了解物种是如何成为害虫的，造成经济损失，有时还会传播疾病。我们的目标是要问，一种分布在全球的鸟类——麻雀——成功的秘诀，是否与它利用自身基因组对抗寄生虫的方式有关。地球上没有任何地方是安全的，所以当动物在新的地方殖民时，它们必须杀死或控制新的寄生虫，否则入侵就会失败。初步数据显示，家麻雀有一种特殊的能力，可以通过一种叫做DNA甲基化的过程来调节它们的免疫系统。我们把这种能力比作收音机上的旋钮；旋钮越多，音质控制就越精细。对于家麻雀来说，更成功的鸟类似乎在它们的基因组中有更多的旋钮，我们希望这有助于它们调整免疫基因的表达，从而更好地控制新的寄生虫。有了这笔拨款，我们将进行实验，直接测试更多的基因组控制旋钮是否意味着对感染的更好保护，然后我们将比较本地和引进的麻雀群体之间的基因组旋钮数量，期望入侵鸟类中有更多的旋钮。我们还将研究博物馆收藏的麻雀，询问自19世纪50年代首次引入以来，旋钮数量是如何变化的。我们的计划是利用家麻雀（Passer domesticus）的近普遍性来了解基因调控区域的CpG（即DNA序列中靠近鸟嘌呤的胞嘧啶）含量如何影响这种鸟类的分布。CpG含量，我们称之为表观遗传潜力（EP），可能允许基因型在几代内可逆地掩盖和表现表型可塑性，因为一些CpG位点在甲基化时改变了基因表达。为了支持这一观点，初步数据显示：i)引进的麻雀种群在两个免疫基因启动子上的CpG位点比本地种群多；ii)在四个独立种群中，启动子（而非外显子）的EP自170年前引进以来有所下降。我们认为EP代表了一种适应潜力，为生物体提供了一种应对新环境的倾向。特别是，我们预计EP对toll样受体的调节是重要的，toll样受体是驻留在白细胞上和白细胞内的主要微生物监视机制。在一系列的实验和描述性田野和博物馆研究中，我们将探讨EP、DNA甲基化和TLR表达在个体麻雀中的关系，TLR的EP是否对肠道微生物感染有保护作用，TLR中的EP是否影响正在进行的范围扩展中的肠道微生物群落，最后，TLR的EP是否对范围扩展具有重要意义。适应潜力这个术语，指的是生物体应对或利用新环境的潜在能力。我们的建议的核心概念，EP，可以是一种可测量的适应潜力形式，适用于许多动物系统。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Some species have managed to colonize much of the planet, but others have narrow geographic ranges. Answering why some species can live so many places is interesting to basic biology, namely because it reveals the details of evolutionary processes. However, this form of research also has practical value, as it could help us understand how species come to be pests, causing economic damage and sometimes spreading disease. Our goal here is to ask if the secret to the success of one globally-distributed bird, the house sparrow, has to do with the way it uses its genome to combat parasites. No place on Earth is safe from infection, so when animals colonize new places, they must kill or control new parasites, or the invasion fails. Preliminary data show that house sparrows have an exceptional ability to adjust their immune systems via a process called DNA methylation. We liken this ability to knobs on a radio; more knobs mean more sophisticated control of sound quality. For house sparrows, more successful birds seem to have more knobs in their genomes, which we expect helps them adjust their immune gene expression and thus control especially new parasites well. With this grant, we’ll perform experiments to test directly if more genome control knobs mean better protection from infections, then we’ll compare genome knob number between native and introduced groups of sparrows, expecting more knobs in invading birds. We’ll also study sparrows in museum collections, asking how knob number has changed since introductions first happened in the 1850s.Our plan is to leverage the near-ubiquity of the house sparrow (Passer domesticus) to learn how the CpG (i.e., cytosines proximal to guanines in DNA sequences) content of gene regulatory regions influenced the distribution of this avian species. CpG content, something we term epigenetic potential (EP), might allow genotypes to mask and manifest phenotypic plasticity reversibly within generations, as some CpG sites alter gene expression when methylated. In support, preliminary data reveal that i) introduced sparrow populations have more CpG sites in two immune gene promoters than native populations, and ii) EP in promoters, but not exons, declined since introduction ~170 years ago in four independent populations. We expect that EP represents a form of adaptive potential, providing organisms with a propensity to cope with the novel conditions. In particular, we expect EP to be important to the regulation of Toll-like receptors, major microbial surveillance mechanisms that reside on and in leukocytes. In a series of experiments and descriptive field and museum studies, we will ask how are EP, DNA methylation, and TLR expression related within individual sparrows, whether EP for TLRs protective against gut microbial infections, if EP in TLRs influences gut microbial communities in ongoing range expansions, and finally whether EP for TLRs important to range expansions historically? The term, adaptive potential, connotes a latent ability of organisms to cope with or exploit novel conditions. The core concept of our proposal, EP, could be one measurable form of adaptive potential, applicable to many animal systems.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.