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Surfing the dynamics in genomes: Regulation of moved genes in Drosophila and the expansion of an apoptosis regulatory gene family in eukaryotes.

机译:冲浪基因组中的动力学:果蝇中移动的基因的调控和真核生物中凋亡调控基因家族的扩展。

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摘要

It is well accepted that genomes are dynamic. Genomes can be reorganized by gene duplications and chromosomal rearrangements. Gene duplications are mediated by either DNA- or RNA-based mechanisms. The latter give rise to retrotransposed genes (retrogenes) via reverse transcription from mRNA without the original regulation. Chromosomal rearrangements, while not normally generating duplicated copies, do move genes to new locations. The breakpoints of rearrangements can disrupt the regulatory region of nearby genes. Thus the functional expression of any retrotransposed or moved genes raises the question as to how they are regulated after drastic changes in their genomic environment.;The twelve fully sequenced Drosophila genomes provide an excellent dataset to study the regulation of lineage-supported retrogenes and genes moved via chromosomal rearrangements. Orphan retrogenes, whose parental copies have been lost or have degenerated into pseudogenes, are a particular class of retrogenes studied here. The primary aim of this dissertation is to investigate the transcriptional regulatory signals associated with such retrotransposed and moved genes. An efficient computational approach based on the Branch-and-Bound algorithm is implemented to seek the most informative ordered common cis-regulatory elements among the orthologues of these genes. Such a comparison can identify the regulatory signals that are common to all or specific to either the parent or the moved copy. From the examples explored, I have proposed the mechanisms by which retrotransposed and moved genes could be regulated to carry out the original functions and thus be retained in their new genomic environments.;The second aim of the dissertation is to delineate the duplicative expansion of an apoptosis regulatory gene family in a wide spectrum of eukaryote genomes. Most of these genes are currently unannotated or have been subsumed under two questionably related gene families. A detailed sequence and phylogenetic analysis shows that only five of them form a clear and unique gene family, which I named Lifeguard (LFG). My analysis provides information for understanding the specific biological roles of these proteins across a wide range of tissues in model organisms. The evolutionary relationships among LFG genes can provide a powerful prospect for extrapolating to human conditions.
机译:基因组是动态的,这是公认的。基因组可以通过基因重复和染色体重排而重组。基因重复是通过基于DNA或RNA的机制介导的。后者通过从mRNA逆转录而产生逆转座基因(逆转录基因),而没有原始调控。染色体重排虽然通常不产生重复的拷贝,但是确实将基因移到了新的位置。重排的断裂点可以破坏附近基因的调节区域。因此,任何逆转位或转移的基因的功能性表达提出了一个问题,即它们在其基因组环境发生急剧变化后如何受到调节。;十二个完全测序的果蝇基因组提供了一个极好的数据集,用于研究谱系支持的逆转录基因和转移的基因的调控通过染色体重排。其亲本拷贝已丢失或退化成假基因的孤儿逆转录酶是此处研究的一类特定的逆转录酶。本文的主要目的是研究与这种逆转座和移动基因相关的转录调控信号。实现了一种基于分支定界算法的有效计算方法,以在这些基因的直向同源基因中寻找信息量最大的有序普通顺式调控元件。这样的比较可以识别所有或特定于母体或移动副本通用的调节信号。从所研究的实例中,我提出了调控逆转座和移动基因以执行其原始功能并因此保留在其新基因组环境中的机制。论文的第二个目的是描述一个基因的重复扩增。广泛的真核生物基因组中的凋亡调控基因家族。这些基因中的大多数目前未注释,或已归入两个可疑相关的基因家族之下。详细的序列和系统发育分析表明,它们中只有五个形成了清晰而独特的基因家族,我将其命名为Lifeguard(LFG)。我的分析为了解这些蛋白质在模型生物体内广泛组织中的特定生物学作用提供了信息。 LFG基因之间的进化关系可以为推断人类状况提供强大的前景。

著录项

  • 作者

    Hu, Lan.;

  • 作者单位

    Boston University.;

  • 授予单位 Boston University.;
  • 学科 Biology Bioinformatics.
  • 学位 Ph.D.
  • 年度 2010
  • 页码 123 p.
  • 总页数 123
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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