BRC-BIO: Evolutionary Genomics of Atadenoviruses

提高我们对病毒进化的认识对于预测哪些病毒对人类和动物健康构成威胁至关重要。能够感染多种宿主物种的病毒特别令人感兴趣，因为它们可能最有可能在广泛的物种之间传播。该项目的目标是获得关于腺病毒进化的新见解，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执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-卡姆登大学的学生个人将受益于直接接触先进的基因组学研究和开发新的动手进化课程，这将使本科生接触到现代进化基因组学研究。本研究也将有助于进一步了解腺病毒的进化以及生态群落与病毒自然选择之间的关系。这项工作的结果将极大地增加这组病毒的基因组数据，使进一步的基础和应用研究目标成为可能。从样本丰富的病毒进化枝中获得健壮的、基因组规模的系统发育是推断宿主转换速率所必需的。虽然腺病毒通常被认为是与宿主共同进化的，但这一群体中的一个属——腺病毒——却违背了这一趋势，感染了不同种类的脊椎动物宿主。该项目包括三个目标，1)评估Atadenovirus宿主的真正宽度，2)推断该属的系统发育及其宿主切换率，3)扩展这些分析以检测自然选择的分子特征和测试Anolis蜥蜴的加速适应性分子进化，这一群体可能特别容易发生Atadenovirus宿主切换。为了评估被Atadenoviruses感染的宿主的广度，将收集来自整个鳞状动物生命树的样本，检测Atadenoviruses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Atadenoviruses的系统发育，将对基因组序列进行比对，并通过物种树系统发育分析推断出它们之间的关系。然后，系统发育比较方法将用于测试对腺病毒宿主转换速率的预测。为了描述Atadenoviruses及其宿主的进化基因组学特征，上述系统发育树和排列将用于对atadenovirus及其爬行动物宿主进行自然选择的独立测试。这些分析将用于验证预测的高密度和物种丰富度导致加速病毒和宿主受体的进化。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。

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.