Genomic Analyses of Intraspecific Patterns of Extreme Recombination in Honey Bees

描述(申请人提供)：我的长期目标是以蜜蜂为科学模型，在基因组水平上理解社会进化的原因和后果。到目前为止，在蜜蜂身上发现的最重要的基因组特征是它们异常高的基因组重组率。蜜蜂基因组重组率的强烈上调尚未得到详细的研究，尽管对其模式和机制的研究可能会为我们理解DNA重组提供相关的见解，并对DNA修复、基因组稳定性、癌症生物学、病原体的遗传变异，从而对人类健康产生影响。基于以前的发现，蜜蜂在所有后生动物中表现出最高的基因组重组率，以及单个蜜蜂女王的大量后代，我建议详细研究蜜蜂基因组中的重组模式。该项目将检验这样的预测，即蜜蜂极高的重组率与重组的高度可变性有关，这是由于最近提出的减数分裂重组调节的进化动力学。这一预测将通过解决以下三个具体目标来验证：1.利用经济高效的RAD-Tag标记构建首个意大利蜜蜂高密度连锁图谱，以研究重组的细微尺度模式和表征重组热点。2.通过对90个不同居群的不同蜂王后代的选择连锁标记进行基因分型，鉴定了意大利蜜蜂特定基因组区域内重组率的种内变异。3.通过比较氧化应激前后年青、老年蜂王后代和蜂王后代的重组率，研究所选基因组区域重组率的个体内变异。在最近方法学的进步和对基因组重组调控的兴趣的推动下，这项建议是及时的和创新的。它阐述了一个与人类健康有多种联系的基本生物过程。它将提供新的见解，阐明特定的研究系统，但也有助于我们对减数分裂重组及其变异性的一般理解。它将产生数据，以产生新的假设，作为未来研究的基础。此外，这项研究的资金将加强联合国教科文组织生命科学的研究环境，特别是在我们系新设立的博士课程方面。最后，这将使我能够更多地致力于指导学生研究和培养下一代生命科学家。 与公共健康相关：除了作为传粉者的重要性，蜜蜂还可以告诉我们DNA重组，这是一个与多种遗传疾病和癌症有关的过程。这个研究项目将研究蜜蜂的过度重组率，以了解它与人类重组的可比性。它还将研究衰老和压力对重组的影响，以得出可能适用于理解人类基因组完整性的一般性结论。此外，我还将培训和指导学生进行生物医学研究，以促进下一代生命科学家的发展。

DESCRIPTION (provided by applicant): My long-term goal is to understand causes and consequences of social evolution at the genome level, using honeybees as scientific model. The most important genomic feature discovered in honeybees so far is their exceptionally high genomic recombination rate. The strong up regulation of the genomic recombination rate in honeybees has not been studied in detail, although the investigation of its patterns and mechanisms may yield relevant insights for our understanding of DNA recombination with implications for DNA repair, genomic stability, cancer biology, genetic variation of pathogens, and thus human health. Based on the previous finding that honeybees exhibit the highest genomic recombination rate of all metazoans and the large offspring number of individual honeybee queens, I propose to study the patterns of recombination in the honeybee genome in detail. The project will test the prediction that the extraordinarily high recombination rate in honeybees is associated with a high variability in recombination due to the recently proposed evolutionary dynamics of the regulation of meiotic recombination. The prediction will be tested by addressing the following three specific aims: 1. Construction of the first high-density linkage map for A. mellifera with cost-effective RAD-tag markers to study the fine-scale patterns of recombination and characterize recombinational hotspots. 2. Characterization of intra-specific variation in recombination rate in A. mellifera in specific genome regions by genotyping selected linked markers in offspring of 90 different queens from different populations. 3. Study of the intra-individual variation of recombination rates in selected genome regions by comparing recombination rates between linked markers in offspring of young and old queens and from queens before and after oxidative stress exposure. Motivated by recent methodological advances and interest in the regulation of genomic recombination, this proposal is timely and innovative. It addresses a fundamental biological process with multiple connections to human health. It will provide novel insights that illuminate the particular study system but also contribte to our general understanding of meiotic recombination and its variability. It will produce data to generate new hypotheses as basis for future research. Furthermore, funding for this research will strengthen the research environment in the life sciences at UNCG, particularly with respect to the newly established PhD program in our department. Finally, it would allow me to expand my dedication to mentoring student research and fostering the next generation of life scientists. PUBLIC HEALTH RELEVANCE: In addition to its importance as pollinator, the honeybee can also inform us about DNA recombination, a process that is related to multiple genetic disorders and cancer. This research program will study the excessive recombination rate of honeybees to learn how comparable it is to human recombination. It will also study how recombination is affected by aging and stress to draw general conclusion that may be applicable to understand genome integrity in humans. Furthermore, I will train and mentor students in biomedical research to promote the next generation of life scientists.