Pathogen adaptation to specific host genotypes: Implications for host-pathogen coevolution

该奖项是根据2009年美国复苏和再投资法案（公法111-5）资助的。哺乳动物，包括人类，在涉及免疫系统的基因中具有极高的遗传多样性。个体之间产生的差异被认为有助于降低影响人群的传染病的严重程度。但是发生这种情况的机制尚不完全清楚。一种主要的解释是，宿主和病原体在所谓的分子军备竞赛中不断进化，以战胜对方。缺乏足够遗传变异的宿主群体往往会失去这种竞争，因为它更容易受到有毒病原体进化的影响。这项研究通过允许两种病毒在许多代中适应特定的宿主菌株来验证这一假设的预测，并测试由此产生的病原体是否更具毒性及其原因。这项研究的更广泛影响包括提高对病原体引起的人类、农业物种和野生动物健康问题的理解，包括生物恐怖主义制剂在内的新出现疾病的演变，以及减少病原体对濒危物种的影响。在未来20年里，气候变化和其他人类活动将导致地球上大约四分之一的脊椎动物物种濒临灭绝。这些濒临灭绝的物种遭受着遗传多样性的减少，它们重新引入的成功率只有可怜的11%，部分原因可能是病原体的快速进化。该项目首次在脊椎动物中直接验证了这一假设，并为确定减缓毒性病原体进化所需的关键宿主遗传多样性提供了基础。该项目还在跨学科背景下为众多学生提供培训和就业机会。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).Mammals, including humans, have extremely high genetic diversity among the genes involved in the immune system. The resulting differences among individuals are thought to help reduce the severity of infectious diseases affecting a population. But the mechanisms whereby this occurs are not fully known. One leading explanation is that hosts and pathogens are constantly evolving to outmaneuver each other in a so-called molecular arms race. A host population that lacks sufficient genetic variation would tend to lose this race because it would be more susceptible to the evolution of virulent pathogens. This study tests predictions of this hypothesis by allowing two viruses to adapt to specific host strains over many generations, and testing whether the resulting pathogens are more virulent and why. The broader impacts of this research include improved understanding of pathogen-caused health problems for humans, agricultural species and wildlife, the evolution of emerging diseases including bioterrorism agents, and reducing the impact of pathogens on endangered species. Climate change and other human activities will cause an estimated ¼ of earth's vertebrate species to become endangered during the next 20 years. These endangered species suffer reduced genetic diversity and the dismal 11% success rate for their reintroduction may be due in part to rapid evolution of pathogens.This project for the first time directly tests this hypothesis in vertebrates and provides the groundwork for identifying critical host genetic diversity needed to slow the evolution of virulent pathogens. This project also provides training and employment for numerous students in an interdisciplinary context.