【作者】 杨亮；

【导师】 于军；

【作者基本信息】 浙江大学 ， 生物学， 2007， 博士

【摘要】 一直以来,我们都知道基因组的结构具有重要的生物学意义,与基因的转录调控有密切的关系。最典型的例子就是原核生物中的操纵子(operon),通常认为操纵子中的基因基本上都有功能上的相关性,而且这种结构有效的保证了基因的共调控(coregulation)。在真核生物基因组中,尽管缺少操纵子结构,但是通过比较基因组学的分析,越来越多的证据表明基因顺序和相对位置的保守性是的确存在的,也就是说基因在染色体上不是随机分布的。这种基因分布的非随机性是与一级结构和染色体上的调控相关的,并且在进化中有一定的选择优势(selection advantage)。双向转录基因对(divergent gene pairs)指的是两个相邻的基因,它们转录方向相反(divergently transcribed)并且转录起始位点(transcription start site,TSS)的距离不超过1000个碱基。随着大量实验证据的出现,双向转录基因对越来越被认为是基因组中普遍存在的现象。但是,对其在全基因组范围上的细致研究还不是很多。由于双向转录基因对在启动子区域可能共用一些调控元件,这个区域里的突变可能会改变两个基因的启动子活性,从而影响两个基因的共表达转录,所以研究双向转录基因对的形成机制,进化过程,共表达的关系,功能分布以及双向转录启动子的特点对于我们深刻理解这种基因组结构具有很重要的意义。本文通过对果蝇基因组中的双向转录基因对的系统分析以及与其他以人类为代表的真核生物基因组进行比较研究,发现双向转录基因对的结构在所有真核生物中部是普遍存在的。同时,相对于基因组的基因密度(gene density),果蝇基因组中则比其他真核生物基因组具有更高比例的双向转录基因对。比较基因组学的分析又表明在一定的进化时间范围内,双向转录基因是很保守的。不同基因组中的双向转录基因对很可能是在进化过程中相互独立的发展起来的。另外,基因表达分析也显示果蝇基因组中的大部分双向转录基因对都是具有显著的表达相关性的。更进一步,双向转录基因对更倾向于具有很强的功能上的相关性,而且存在着潜在的调控作用关系。最后,我们还发现双向转录基因通常都是管家基因(housekeeping gene)而且在双向转录启动子中不含有TATA-box。果蝇基因组中,核心启动子Initiator(Inr)和Downstream Promoter Element(DPE)的组合在调控双向转录基因对结构中可能起到重要的作用。更多还原

【Abstract】 It has long been known that the gene organization is one of the important biological information and strongly associated with gene transcriptional regulation. The most well-known example is prokaryotic operons,which ensure effective gene coregulation.Generally presumed,genes within an operon are ahnost always functional associated.Despite the rarity of an operon structure in eukaryotes,more and more evidence by comparative genomics indicate that gene order is indeed conserved during the evolution,suggesting that genes are not randomly distributed on the chromosome.The non-random gene distribution is associated with the regulation of sequence and chromosome structures and has selection advantages during the genome evolution.Divergent(or "bidirectional")gene pair is defined as two adjacent genes which are divergently transcribed on opposite strands of DNA with transcription start sites (TSSs)not more than 1000 base pairs apart.Divergent gene pairs are considered as common phenomena since lots of individual experimental evidences have been reported.Only a few genome-wide analyses have been studied in detail.The mechanism and evolution of this gene organization is of great interest because a mutation in the region between divergent gene pairs would cause changes in the promoters of both genes and affect the co-regulated transcription of the pairs.We conducted comprehensive analysis of divergent gene organization in Drosophila genomes and comparision with other eukaryotic genomes.The enrichment of divergent gene pairs was found in all the eukaryotes.However,D.melanogaster had significantly higher proportion of divergent gene pairs relative to its gene density than the other eukaryotes.The results obtained by comparative genomics indicated that the divergent gene pairs were conserved on a certain scale of evolution.The divergent gene arrangement seems to have arisen independently each other during the evolution. The expression analysis showed that most of divergent gene pairs in D.melanogaster were significantly correlated.Furthermore,divergent gene pairs were likely to have strong functional association and potential regulatory interactions.Finally,we found the divergent genes usually perform housekeeping role and have no TATA box in shared promoter region.The combination of Initiator(Inr)and Downstream Promoter Element(DPE)may play an important role in regulating the divergent gene organization in D.melanogaster,just like CpG islands for mammals.更多还原