The Causes and Consequences of Complementation and Selfishness in Viruses

病毒中互补性和自私性的原因和后果

• 批准号: 7332810
• 负责人: SARAH BETH JOSEPH
• 金额: $ 4.68万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7332810
• 关键词: Affect; Alleles; Bacteriophages; Biological Models; Cells; Class; Data; Diploidy; Drug resistance; Evolution; Frequencies; Genes; Genetic; Genotype; Haploidy; Human; Infection; Masks; Measures; Methods; Mutation; Nature; Nucleic Acid Regulatory Sequences; Numbers; Pathogenesis; Physiological; Population; Production; Resource Sharing; Site-Directed Mutagenesis; Structural Genes; Testing; Viral Pathogenesis; Virulence; Virus; base; cost; fitness; insight; pathogen; research study; sample fixation; theories

DESCRIPTION (provided by applicant): When two viruses infect a single host cell, they interact in ways that influence their evolution and pathogenesis. I will investigate two such interactions: 1) complementation, the masking of an allele carried by one virus by the homologous allele carried by the other virus, and 2) selfishness, the exploitation of a shared resource by one allele at a cost to the homologous allele. These interactions allow the persistence of mutations that reduce fitness (i.e. deleterious and selfish mutations), and slow the fixation of beneficial mutations. Although complementation and selfishness have been observed to affect the evolution of drug resistance and virulence in particular cases, the general nature of these interactions and the frequency with which they arise in viruses has not been studied. I will conduct evolution experiments to examine the causes and fitness consequences of complementation and selfishness in the bacteriophage 96. Specific Aim 1. Determine whether the physiological theory of dominance accurately predicts the effects of complementation in viruses. I will perform two sets of experiments to test this. The first will examine the relationship between dominance and selection coefficients of deleterious mutations to determine whether, as predicted by the physiological theory of dominance, they are negatively correlated. The second will examine this relationship for beneficial mutations accumulated in populations where viruses are haploid. Specific Aim 2: Determine whether the genetic basis of adaptation differs between haploid and diploid populations. I will examine this in two ways. First, I will determine whether adaptive mutations accumulated in diploid populations are more often selfish than those accumulated in haploid populations. Second, I will measure the dominance coefficients of beneficial mutations accumulated in populations where viruses are effectively diploid (i.e. host cells are typically infected by two viruses). I will then use data from this second experiment to test whether adaptive mutations accumulated in diploid populations are, as predicted by Haldane's Sieve, more dominant that mutations accumulated in haploid populations. Relevance: Interactions between viruses during dual infections may affect the virulence of infections and the evolution of drug resistance. As a result, understanding these interactions in bacteriophage may provide insights into the evolution and pathogenesis of viral pathogens of humans.

描述（由申请人提供）：当两种病毒感染单个宿主细胞时，它们以影响其进化和发病机理的方式相互作用。我将研究两种这种相互作用：1）互补，一种由一种病毒携带的同源等位基因所携带的等位基因掩盖，而另一种病毒携带的同源等位基因，以及2）自私，一个等位基因对同源等位基因的代价剥削共享资源。这些相互作用允许突变的持久性降低适应性（即有害和自私的突变），并减慢有益突变的固定。尽管已经观察到互补和自私会影响耐药性和毒力的演变，但这些相互作用的一般性质以及它们在病毒中出现的频率尚未被研究。我将进行进化实验，以检查噬菌体中互补和自私的原因和适应性的后果。96。具体目的1。确定优势的生理理论是否准确地预测了互补性在病毒中的影响。我将执行两组实验来测试这一点。第一个将检查有害突变的主导地位与选择系数之间的关系，以确定占主导地位生理理论的预测，它们是否存在负相关。第二个将研究这种关系，以在病毒是单倍体的种群中积累的有益突变。具体目标2：确定适应的遗传基础是否在单倍体和二倍体种群之间有所不同。我将通过两种方式进行检查。首先，我将确定在二倍体种群中积累的自适应突变比在单倍体种群中积累的自适应更为自私。其次，我将测量在病毒有效二倍体（即宿主细胞通常被两种病毒感染的人群中）积累的有益突变的主导系数。然后，我将使用第二个实验中的数据来测试二倍体种群中积累的自适应突变，如Haldane的筛子所预测的那样，比单倍体种群中积累的突变更为主导。相关性：双重感染期间病毒之间的相互作用可能会影响感染的毒力和耐药性的演变。结果，了解噬菌体中的这些相互作用可能会提供对人类病毒病原体的进化和发病机理的见解。