Molecular Mechanisms of Adaptive Evolution in Pathogen Populations

病原体种群适应性进化的分子机制

• 批准号: 0542904
• 负责人: Raymond St.Leger
• 金额: $ 39.45万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0542904&HistoricalAwards=false
• 关键词: Molecular; Mechanisms; Adaptive; Evolution; Pathogen

This research will address a central question in pathogen biology about which we know little: what types of changes in what types of genes account for the emergence of host specificity? The entomopathogenic fungus Metarhizium anisopliae provides an excellent model system for studying this question. It is a radiating species, and contains both generalist and specialized lineages with broad and narrow host ranges. Strains representing evolutionary distances ranging from 1 to11 million years can be selected and their natural molecular variation allows analysis of processes of both adaptive change and phylectic differentiation still in operation, even in intermediate states. To investigate how regulatory variation and changes in gene content contribute to infection characteristics, cDNA or DNA from generalist and specialist strains will be co-hybridized to thousands of ESTs expressed during infection processes by a reference strain. This will: 1) investigate the contribution to pathogenic specialization of gene duplication, divergence and degradation, and 2) identify pseudogenes that will provide a unique dataset to study the role of neutral sequence evolution in a fungus and its underlying mutational processes in different lineages. Using atlases of gene expression, combined with technologies to modulate mRNA levels, the investigator will explore the extent to which control of gene expression is used as a vehicle by evolution to define the host range of multiple strains. In further experiments he will look at the role of regulatory genes, including several that may play a role in host switching.In terms of broad impact, genetic variation is a powerful tool to study the molecular basis of adaptation (one of the "Holy Grails" of evolutionary biology) and the questions being asked here on the mechanisms by which novel pathogens emerge address many basic, yet poorly understood issues that span much of molecular evolution. Addressing these issues will greatly increase our knowledge of the mechanisms by which new pathogens emerge with either wide or narrow host ranges. It will also greatly increase our knowledge of the dynamics of a fungal genome and help define the appropriate evolutionary distances for answering questions on mutation rates, gene degradation and modulation of gene expression. This will help establish a foundation for comparative genomics and inform optimal choices for broader sampling of fungal genomes. The project will also provide research opportunities for a postdoctoral fellow, graduate students and undergraduate students from underrepresented groups.

这项研究将解决病原体生物学中我们知之甚少的一个核心问题：哪些类型的基因的哪些类型的变化导致了宿主特异性的出现？昆虫病原真菌绿僵菌为研究这个问题提供了一个极好的模型系统。它是一种辐射物种，包含通用谱系和特殊谱系，宿主范围有宽有窄。可以选择代表 1 至 11 百万年进化距离的菌株，它们的自然分子变异允许分析仍在运行的适应性变化和系统分化过程，甚至在中间状态。为了研究基因内容的调控变异和变化如何影响感染特征，来自通用菌株和专用菌株的 cDNA 或 DNA 将与参考菌株在感染过程中表达的数千个 EST 进行共杂交。这将：1）研究基因复制、分化和降解对致病特化的贡献，2）识别假基因，这些假基因将提供独特的数据集来研究中性序列进化在真菌中的作用及其在不同谱系中的潜在突变过程。利用基因表达图谱，结合调节 mRNA 水平的技术，研究人员将探索基因表达控制在多大程度上被用作进化的工具来定义多种菌株的宿主范围。在进一步的实验中，他将研究调节基因的作用，包括一些可能在宿主转换中发挥作用的基因。就广泛的影响而言，遗传变异是研究适应的分子基础（进化生物学的“圣杯”之一）的有力工具，这里提出的关于新型病原体出现的机制的问题解决了许多基本的、但人们知之甚少的分子进化问题。解决这些问题将大大增加我们对宿主范围广泛或狭窄的新病原体出现机制的了解。它还将极大地增加我们对真菌基因组动力学的了解，并有助于定义适当的进化距离，以回答有关突变率、基因降解和基因表达调节的问题。这将有助于建立比较基因组学的基础，并为更广泛的真菌基因组采样提供最佳选择。 该项目还将为来自代表性不足群体的博士后、研究生和本科生提供研究机会。