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

有些物种已经成功地在地球上的大部分地区定居，但其他物种的地理范围很窄。 解释为什么某些物种可以生活在如此多的地方对基础生物学来说是有趣的，也就是说，因为它揭示了进化过程的细节。 然而，这种形式的研究也具有实用价值，因为它可以帮助我们了解物种如何成为害虫，造成经济损失，有时还传播疾病。 我们的目标是想知道，一种全球分布的鸟类，家雀，成功的秘诀是否与它使用基因组对抗寄生虫的方式有关。 地球上没有一个地方是安全的，所以当动物在新的地方定居时，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，家雀具有通过一种称为DNA甲基化的过程来调节其免疫系统的特殊能力。 我们把这种能力比作收音机上的旋钮;更多的旋钮意味着更复杂的音质控制。 对于家雀来说，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，从而很好地控制特别是新的寄生虫。 有了这笔赠款，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更好的保护免受感染，然后我们将比较本地和引入的麻雀群体之间的基因组旋钮数量，预计入侵鸟类中的旋钮更多。 我们还将研究博物馆藏品中的麻雀，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。我们的计划是利用几乎无处不在的家雀（Passer arteriticus）来了解CpG（即，DNA序列中鸟嘌呤附近的胞嘧啶）含量影响该鸟类的分布。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基因表达。作为支持，初步数据显示，i）引入的麻雀种群在两个免疫基因启动子中具有比天然种群更多的CpG位点，和ii）自170年前引入以来，在四个独立种群中，启动子中的EP而不是外显子中的EP下降。我们认为EP代表了一种适应性潜能，为生物体提供了科普新条件的倾向。特别是，我们预计EP是重要的调节Toll样受体，主要微生物的监视机制，驻留在白细胞上和中。在一系列的实验和描述性的领域和博物馆的研究，我们将问如何EP，DNA甲基化和TLR表达相关的个体麻雀，是否EP的TLR保护肠道微生物感染，如果EP的TLR影响肠道微生物群落在正在进行的范围扩张，最后是否EP的TLR重要的范围扩张的历史？适应潜能这个术语意味着生物体科普或利用新条件的潜在能力。我们建议的核心概念，EP，可能是一种可衡量的形式的适应潜力，适用于许多动物system.This奖项反映了NSF的法定使命，并已被认为是值得通过评估使用基金会的智力价值和更广泛的影响审查标准的支持。

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.