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Understanding the Meiotic Recombination Rate Heterogeneity in Caenorhabditis elegans.

机译:了解秀丽隐杆线虫的减数分裂重组率异质性。

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摘要

Understanding the heterogeneity in meiotic recombination rates is imperative, in light of its multifaceted role in affecting adaptive evolution and shaping genetic diversity within a population. This work is focused on studying the fine-scale (a resolution of a few kilobasepairs) variation in meiotic recombination rates in Caenorhabditis elegans in an effort to understand the mechanistic and evolutionary forces shaping the genetic diversity in this organism.;The C. elegans chromosomes (five autosomes and an X chromosome) show a reproducible pattern of low recombination in the center of the chromosome versus high recombination in the chromosome arms, distinguished by pronounced boundary regions. The causes underlying this distinct domain structure are unknown. Using C. elegans strains with a wild-type chromosomal complement for targeted genetic crosses in conjunction with dense molecular genotyping, a high-resolution recombination rate map of the chromosome 2 center-right arm recombination rate boundary region was generated. The wildtype distribution of crossovers in this 2.275 Mb region is characterized by well-defined large-scale domains with limited fine-scale rate heterogeneity. In fact, using the Gini coefficient as a summary statistic we found that this region had the least heterogeneous fine-scale distribution among the model organisms with comparable crossover distribution data available, and that our data for this region was incompatible with a mammalian-type hotspot-rich recombination landscape. The large-scale domains of recombination rate variation in this region are separated by a discrete boundary, which we localize to a small region. Our comparison of this high-resolution recombination rate map to the currently known distributions of genomic features in the C. elegans genome showed that the recombination rate boundary coincided with the arm-center boundary defined both by nuclear-envelope attachment of DNA in somatic cells and GC content. These observations are consistent with proposals that these features of chromosomal organization may be mechanical causes and evolutionary consequences of meiotic recombination.;To explore the individual contributions of local sequence features and the chromosome-wide recombination rate domain structure in dictating the crossover distribution in this region we measured the fine-scale recombination rate variation in alternative chromosomal context using whole chromosome fusion strains. We show that both sequence features and chromosomal context shape the fine-scale crossover distribution in this region. We observed that the crossover distributions measured in the contrasting chromosomal context were strikingly conserved, indicating the role of sequence in shaping this rate heterogeneity. Our comparison of the fusion and wildtype karyotype fine-scale crossover distributions along with the chromosome-wide crossover distributions allow us to uncouple the role of sequence and chromosome-wide domain structure in shaping the pattern of crossover distribution in this region of the C. elegans genome.;In order to understand the pattern of linkage disequilibrium, a reliable readout of natural selection, mutation, gene conversion, population structure and level of outcrossing in a population, knowledge of the recombination rate variation in the genomic region is crucial. The high-resolution empirical measures of recombination rates from this study make possible future investigations to explicitly test theoretical predictions of the relationship between linkage disequilibrium and recombination rate variation in C. elegans.
机译:鉴于减数分裂重组率在影响适应性进化和塑造种群遗传多样性方面具有多方面的作用,因此必须了解减数分裂重组率的异质性。这项工作的重点是研究秀丽隐杆线虫的减数分裂重组率的精细尺度(几千个碱基对的分辨率)变化,以了解影响该生物遗传多样性的机制和进化力。秀丽隐杆线虫染色体(5个常染色体和X染色体)显示了可重现的模式,即在染色体中心的低重组与在染色体臂中的高重组,以明显的边界区域为特征。这种独特的域结构的根本原因尚不清楚。使用具有野生型染色体补体的秀丽隐杆线虫菌株进行定向遗传杂交并结合密集的分子基因分型,生成了第2号染色体中心-右臂重组率边界区域的高分辨率重组率图。在2.275 Mb区域中,交叉的野生型分布的特征是定义良好的大规模域,有限的精细速率异质性。实际上,使用基尼系数作为汇总统计数据,我们发现该区域在模型生物中具有最小的异质精细尺度分布,并且具有可比较的交叉分布数据,并且该区域的数据与哺乳动物类型的热点不兼容。丰富的重组格局。该区域中重组率变化的大规模域由离散边界分隔,我们将边界定位在一个较小的区域。我们对该高分辨率重组率图谱与秀丽隐杆线虫基因组中当前已知的基因组特征分布的比较表明,重组率边界与臂核边界重合,臂臂边界是由体细胞中DNA的核包被和GC含量。这些观察结果与以下观点相符:染色体组织的这些特征可能是减数分裂重组的机械原因和进化结果。;探讨局部序列特征和整个染色体重组率域结构在决定该区域交叉分布方面的个体贡献我们使用完整的染色体融合菌株在替代染色体环境中测量了精细重组率变化。我们表明,序列特征和染色体上下文都在该区域内形成了精细的交叉分布。我们观察到,在对比的染色体环境中测得的交叉分布显着保守,表明序列在塑造此速率异质性中的作用。我们对融合和野生型核型细尺度交叉分布以及全染色体交叉分布的比较使我们能够解开序列和全染色体域结构在塑造秀丽隐杆线虫这一区域的交叉分布模式中的作用为了了解连锁不平衡的模式,可靠地读出自然选择,突变,基因转换,种群结构和种群中的异交水平,了解基因组区域的重组率变异至关重要。这项研究的高分辨率重组率的经验方法使将来的研究成为可能,以明确检验线虫连锁不平衡与重组率变化之间关系的理论预测。

著录项

  • 作者

    Kaur, Taniya.;

  • 作者单位

    New York University.;

  • 授予单位 New York University.;
  • 学科 Biology Genetics.;Biology Molecular.;Biology General.
  • 学位 Ph.D.
  • 年度 2014
  • 页码 111 p.
  • 总页数 111
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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