QQ客服 官方微博 反馈留言

题名	基因组中新遗传结构的起源与进化
作者	杨爽
学位类别	博士
答辩日期	2008-01
授予单位	中国科学院研究生院
授予地点	北京
导师	王文
关键词	新基因 新外显子 起源 进化
其他题名	Origin and evolution of genetic novelties
学位专业	动物学
中文摘要	生物遗传物质的多样性从根本上决定了当今地球上生命世界的丰富多彩。然而生命在漫长的进化历程中如何从最原始的生命形态不断演变，创造出如此巨大的多样性，是自然留给我们最吸引人的奥秘之一。因此对于分子进化生物学或进化基因组学的研究者来说，承载生命遗传信息的基因组如何进化一直以来都是大家关注的一个基本科学命题。本研究主要从两个方面探讨了基因组中新遗传结构起源的分子机制和进化模式，一方面我们以实验的方法在黑腹果蝇亚种组中大规模地对新基因进行筛选和鉴定，探讨了果蝇基因组中新基因起源的分子机制和进化模式；另一方面我们以生物信息学手段对啮齿类动物大鼠和小鼠进行比较基因组研究，以人和猪的转录序列作为外群，鉴定了大量啮齿类特有的新外显子，并对这些新外显子的进化特征和产生机制做了研究。 在果蝇基因组新基因起源与进化的研究工作中，我们综合运用了荧光原位杂交(fluorescent in situ hybridization, FISH)，Southern印迹 (Southern blotting)，表达转录分析，生物信息确认和进化速率分析等技术和分析手段，通过对黑腹果蝇约7000个基因在黑腹果蝇亚种组8个近缘物种中同源拷贝数分布的筛选，鉴定了17个年轻的散在重复新基因，并对这些新基因的结构、表达和进化进行了全面的分析。结果表明，DNA水平的重组机制产生了大量的新的与祖先基因结构没有冗余的散在重复基因，它们的基因结构以很高的频率形成了嵌合结构。这些新散在重复基因形成嵌合基因的机会有可能大大高于预期。同时，我们提供了有力证据证明，重复序列特别是DNAREP1转座子很可能通过了非等位同源重组方式介导了散在重复基因的形成。最后，运用多种行之有效的分析方法，我们证明绝大部分的这些新的嵌合重复基因是有功能的。 在啮齿类新外显子的起源与进化研究中，我们首先利用有完整序列信息的人和小鼠的基因组，通过同源比对确定了人和小鼠间12,419个直系同源的基因组转录单元，这些基因组转录单元中71,039个大、小鼠共有且相位定义清晰的外显子被用作后续的分析。通过与人的基因组序列相比较，并进一步以猪的转录组序列作为第二外群排除掉可能是在人的基因组中丢失的外显子后，我们共确定了2,695个啮齿类特有的新外显子。随后对这些新外显子产生的机制、进化速率、潜在功能以及与选择性剪接之间的关系进行了讨论。结果显示多数新外显子来自内含子的非重复序列，存在快速的碱基非同义替换和插入缺失，功能分布上最多的是参与细胞外结合和蛋白间相互作用，提示这些新外显子的产生可能与啮齿类与外界环境的适应性进化相关。对这些新外显子与选择性剪接之间关系所做的分析表明，大多数的新外显子存在于表达量较低的选择性剪接形式中，这说明这些外显子通常参与形成执行组织特异功能的表达形式，也从一定程度上解释了这些外显子何以能够摆脱对基因的功能限制而产生较快的进化速度。 总之，上述对果蝇基因组中新基因和啮齿类基因组中新外显子的起源和进化的研究结果表明，基因组中通过新基因或新外显子等基因组新材料产生新功能的进化过程是常见的和重要的遗传机制。
英文摘要	The great bio-diversities on the earth deeply root in the genetic diversities among different species. How such diversities evolve from ‘primeval soup’ during the long-term evolution is one of the most intriguing mysteries of nature. This mystery translates to the question ‘how the genome which bears the genetic information evolves’ for evolutionary biologists. In this work, we sought to answer this fundamental question from two aspects of researches. On one aspect, we systematically screened and characterized new genes of Drosophila melanogaster subgroup species with an experimental approach developed by ourselves. We studied the underlying molecular mechanisms and evolutionary patterns for origin of new genes. On the other hand, we compared transcriptomes of mouse and rat with human and pig as outgroups. Comparative genomic studies enabled us to identify all of the new exons specific to rodent species. We addressed both creation mechanisms and evolutionary characteristics of these new exons with further analyses. In the work of studying new genes in Drosophila, we applied multiple approaches including flurescent in situ hybridization (FISH), Southern blotting, expression assay, bioinformatic validation and evolutionary rates analysis. This integrative work flow enables us identify 17 new dispersed duplicate genes out of about 7000 genes, which are distributed on different branches of the eight species tree with the D. melanogaster subgroup. We revealed that DNA-level recombination has created lots of dispersed new duplicate genes without structure redundancies compared to their ancestors. These new duplicate genes formed new chimeric structures with an unexpected frequency. We also provided strong evidence that the formation of such chimeric structure was mediated by repetive sequences, possiblye through non-allelic homologous recombination. At last, we proved that most of the chimeric new genes are functional with expression assays and evolutionary rate analysis. In the work of studying rodent-specific new exons, we took advantage of genome sequence information of both human and mouse. We first identified 12,419 orthologous genes with transcription evidence between human and mouse. We subjected 71,039 exons of these genes shared by mouse and rat to subsequent analysis. We compared these exons to genome sequence of human and then transcriptome data of pig as a second outgroup to exclude possible exon loss events in human. Then we characterized 2,659 virtual new exons specific to rodents. We studied various aspects of these new exons including their underlying creation mechanisms, evolutionary rates, potential functions and their relationship with alternative splicing. We showed that majority of new exons originated from non-repetitive sequences of introns. They appear accelerated rate of nonsynonymous substitutions and indels. At last, analysis of relationship between new exon and alternative splicing showed most of the new exon reside in isoforms with low expression. It suggests these new exon may be involved in isoforms which execute specific functions and partially explains the fastly-evolved pattern of new exons. Overall, studies on new genes of Drosophila and new exons in rodents provided evidence showing origination of new genes/exons is not rare events and both of them could further contribute to the adaptation of the species with novel functions.
语种	中文
公开日期	2010-10-13
内容类型	学位论文
源URL	[http://159.226.149.42:8088/handle/152453/6080]
专题	昆明动物研究所_基因起源组
推荐引用方式 GB/T 7714	杨爽. 基因组中新遗传结构的起源与进化[D]. 北京. 中国科学院研究生院. 2008.

个性服务

查看访问统计

相关权益政策

暂无数据

收藏/分享

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。