BRC-BIO: Evolutionary Genomics of Atadenoviruses

提高我们对病毒进化的了解对于预测哪些病毒对人类和动物健康构成威胁至关重要。能够感染不同宿主物种的病毒特别令人感兴趣，因为它们可能具有在广泛物种中传播的最大潜力。该项目的目标是获得对阿特腺病毒进化的新见解--阿特腺病毒是一组已知感染爬行动物、哺乳动物和鸟类的病毒。这项工作将通过使用和开发新的基因组测序技术以及进行计算进化基因组学分析来完成。这项研究的潜在影响将是双重的。罗格斯-卡姆登学院的学生个人将受益于直接接触先进的基因组研究和开发一门新的动手进化课程，该课程将使本科生接触到现代进化基因组研究。这项拟议的工作也将有助于增进我们对阿特腺病毒进化以及生态群落和病毒自然选择之间的关系的理解。这项工作的结果将极大地增加这组病毒可用的基因组数据，使进一步的基础和应用研究目标成为可能。因此，从采样充分的病毒分支中获得基因组规模的系统发育图对于推断宿主切换的速度是必要的。虽然腺病毒通常被认为是与宿主共同进化的，但这一组中的一个属--阿特腺病毒--与这一趋势背道而驰，感染了不同的脊椎动物宿主。该项目包括三个目标，1)评估腺病毒宿主的真实广度，2)推断该属的系统发育和宿主转换的速率，3)扩展这些分析以检测自然选择的分子特征和测试Anolis蜥蜴的加速适应分子进化，Anolis蜥蜴是一类可能特别容易进行At腺病毒宿主转换的物种。为了评估被阿特腺病毒感染的宿主的广度，将收集来自鳞状生命树的样本，测试阿特腺病毒的存在，并用于从数百个样本中生成全基因组序列。为了推断阿特腺病毒的系统发育，将对基因组序列进行比对，并使用物种-树系统发育分析来推断关系。然后，系统发育比较方法将被用来测试对AtAdenoVirus宿主转换率的预测。为了描述阿特腺病毒及其宿主的进化基因组学特征，上述系统发育树和比对将被用于对阿特腺病毒及其爬行动物宿主进行独立的自然选择测试。这些分析将被用来检验Anoles的高密度和物种丰富导致病毒和宿主受体加速进化的预测。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

Improving our knowledge of viral evolution is critical to predicting which viruses pose a threat to human and animal health. Viruses that are capable of infecting diverse host species are of particular interest because they may have the greatest potential to move among a broad array of species. The goal of this project is to gain new insights into the evolution of Atadenoviruses – a group of viruses known to infect reptiles, mammals, and birds. This work will be accomplished by using and developing new genomic sequencing techniques and by performing computational evolutionary genomics analyses. The potential impact of this research will be two-fold. Individual Rutgers–Camden students will benefit from both direct access to advanced genomics research and the development of a new hands-on Evolution course that will expose undergraduate students to modern evolutionary genomics research. The proposed work will also serve to advance our understanding of Atadenovirus evolution and the relationship between ecological community and natural selection on viruses. The results of this work will tremendously increase the genomic data available for this group of viruses, enabling further basic and applied research objectives.Robust, genome-scale phylogenies from well-sampled viral clades are necessary to make inferences about the rate of host switching. While Adenoviruses are generally believed to co-evolve with their hosts, one genus within this group – the Atadenoviruses - buck this trend and infect a disparate collection of vertebrate hosts. This project includes three aims, to 1) evaluate the true breadth of Atadenovirus hosts, 2) infer the phylogeny of this genus and the rates of host switching within it, and 3) extend these analyses to detect molecular signatures of natural selection and test for accelerated adaptive molecular evolution in Anolis lizards, a group that may be particularly prone to Atadenoviruses host switching. To evaluate the breadth of hosts infected by Atadenoviruses, samples from across the squamate tree of life will be collected, tested for presence of Atadenoviruses, and used to generate whole genome sequences from hundreds of samples. To infer the phylogeny of Atadenoviruses, genome sequences will be aligned, and relationships inferred using species-tree phylogenetic analyses. Phylogenetic comparative methods will then be used to test predictions about the rate of host switching in Atadenoviruses. To characterize the evolutionary genomics of Atadenoviruses and their hosts, the phylogenetic trees and alignments described above will be used to perform independent tests of natural selection in Atadenoviruses and their reptile hosts. These analyses will be used to test the prediction that the high density and species richness of anoles has led to accelerated viral and host receptor evolution.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.