中文题名: | 拟南芥和琴叶拟南芥中内含子丢失和突变率的关系 |
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学科代码: | 071020 |
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学生类型: | 博士 |
学位: | 理学博士 |
学位年度: | 2013 |
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研究方向: | 进化与比较基因组学 |
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提交日期: | 2013-06-04 |
答辩日期: | 2013-05-30 |
外文题名: | ASSOCIATION OF INTRON LOSS WITH MUTATION RATE IN ARABIDOPSIS THALIANA AND A. LYRATA |
中文摘要: |
尽管内含子丢失是真核生物进化历程中广泛发生的事件,但是作用于内含子丢失的选择压力至今没有得到充分的研究。拟南芥和近缘物种琴叶拟南芥在大约1千万年前分化。之后,拟南芥丢失了大约一半的基因组,同时拟南芥内含子丢失速率显著提高。导致基因组缩小的选择力量被认为同样作用于内含子丢失。但是,基因组缩小的选择压力本身仍然有很大争议。与前人的工作相比,本研究增加了外类群数量,并使用基因序列比对来代替蛋白质序列比对,从而得到了更多的内含子丢失数据。通过使用转录组数据对内含子丢失和内含子获得进行验证,过滤掉没有转录组数据支持的事件,并且过滤掉不满足共线性的候选直系同源基因。这些标准保证了内含子丢失和内含子获得的可靠性。通过对观察到的内含子丢失特征进行分析,并没有找到充分的证据支持逆转录酶介导的内含子丢失。通过非同源末端连接修复双链断裂导致内含子丢失可能是拟南芥和琴叶拟南芥中内含子丢失的主要途径。这两种内含子丢失模型都不可能从突变水平解释拟南芥的内含子丢失频率高于琴叶拟南芥,因此有必要在选择水平探索原因。使用内含子丢失数据进行分析,发现丢失内含子的基因具有更高的同义位点替换率(P = 0.002)。通过分析近缘物种中的同义位点替换率,排除了高突变率是由于其他因素(剪切信号限制消失或缺失导致突变率升高)导致的。通过研究发现内含子之间突变率的差异在拟南芥属和近缘物种间是保守的,因此可以使用近缘物种中的直系同源内含子的核苷酸替换率代表拟南芥属中丢失内含子和现存内含子的突变率。比较发现,丢失内含子的突变率显著高于现存内含子。我们分析了两种内含子中较为常见的调控元件(CpG岛和内含子介导表达量提高的信号),确认丢失内含子和现存内含子突变率的差异不是由于调控元件的多寡造成的。在全基因组水平上,拟南芥的突变率显著高于琴叶拟南芥,与拟南芥的高内含子丢失速率和快速基因组缩小一致。突变率与内含子数量和内含子密度都呈现显著的负相关关系。这些结果表明减少突变风险可能是内含子丢失的选择压力,并且可能也是拟南芥进化过程中基因组缩小的选择压力。小基因组和低内含子密度,被广泛认为和一些表型特征相关,如高新陈代谢速率和快速生长。我们推测,快速增长可能间接的提高突变率,因此突变风险假说可能可以解释基因组大小和各种表型特征的相关性。
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外文摘要: |
Intron losses are common during the evolution of eukaryotes. The selective forces acting on them, however, have not been extensively explored. After the divergence from Arabidopsis lyrata 10 million years ago, Arabidopsis thaliana lost about half of its genome and experienced an elevated rate of intron loss. It is suggested that the selective force acting on genome reduction also has driven intron losses. However, the selective force acting on genome reduction is still in debate.To acquire more intron losses than a previous study, we included more outgroup species and constructed nucleotide alignments, instead of protein alignments. Orthologs that do not present in synteny blocks between species were filtered in order to exclude paralogs from orthologs. The annotations of introns involved in intron losses and intron gains were verified by transcriptome data. The cases that were not supported by transcriptome data were filtered out. The evidence for reverse transcriptase-mediated intron loss is not found from the intron loss dataset. The nonhomologous end-joining repair of double-strand breaks might be the dominant mechanism of intron loss in A. thaliana and A. lyrata. Neither of the models could explain the higher rate of intron loss in A. thaliana than A. lyrata at the mutational level.Intron-lost genes were found to have significantly higher synonymous substitution rates. By analyzing the synonymous substitution rates between closely related species, it is found that the higher substitution rates couldn’t be explained by the abandon of splicing signal or the indel-associated substitution. The differences in mutability among different introns are conserved among Arabidopsis and closely related species, therefore, the nucleotide substitution rates of orthologous introns in closely related species could represent the mutation rates of Arabidopsis introns, either lost or extant. As a result, the mutation rates of lost introns are significantly higher than extant introns. The analyses of two common kinds of regulatory elements, CpG islands and intron-mediated enhancement signals, suggest that the difference between lost introns and extant introns could not be explained by regulatory elements. Comparing to A. lyrata at genome-wide level, A. thaliana has a higher mutation rate, which correlates with the higher rate of intron loss and rapid genome reduction in A. thaliana. Mutation rate is significantly negatively correlated with intron number and intron density. The results indicate that selection to minimize mutational hazards might be the selective force acting on intron loss, and possibly also for genome reduction, in the evolution of A. thaliana.Small genome size and lower genome-wide intron density are considered to correlate with phenotypic features, such as high metabolic rates and rapid growth. By suggesting that selection for rapid growth might indirectly increase mutational hazards, we suggested that the mutational-hazard hypothesis is compatible with these correlations.
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参考文献总数: | 175 |
优秀论文: | |
开放日期: | 2013-06-04 |