从受体的角度研究细胞器基因向细胞核基因组转移的机制

One of the most prominent features of organelle genome evolution is the massive transfer of their genes to the nucleus. In principle, there are three participants in any gene transfer event: the donor (the organelle genome), the being transferred DNA sequence, and the recipient (the nuclear genome). After extensive survey of the literatures, we found that most of the previous studies were focused on the donors and the being transferred genes but overlooked the effects of the recipients: whether they were liable to accept the foreign DNA sequences and how the organelle genes were adapted to the expression system of the nucleus. Taking the advantage of the explosion of genomic data, we will carry out a series of comparative genomic analyses to explore the characteristics of nuclear genomes that influence the insertion of organelle sequences, and examine whether the nuclear genomes whose own sizes are shrinking in evolution are resistant to the insertion of organelle sequences. In addition, we will study the key steps of the domestication of the organelle genes in the nuclear environment: the gain of spliceosomal introns, the recruitment of transit-peptide coding sequence and their influencing factors. Finally, we will comprehensively evaluate all the current hypotheses of organelle genome evolution and try to construct new hypothesis for next-step studies. The results of this project will contribute to the understanding of the evolutionary basis of eukaryotic genetic diversity and give significant implications to the studies of heterosis, cytoplasmic male sterility, and horizontal gene transfer across species as well as the gene therapy of mitochondrial diseases.

内共生起源之后，细胞器基因组进化的最显著特征是：大量基因转移到细胞核中。理论上，基因转移有三个主要参与者：供体（细胞器基因组）、被转移者（DNA片段）和受体（核基因组）。深入调查文献发现，之前研究主要关注供体和被转移者，忽视受体因素的影响。利用基因组数据激增所提供的机遇，本项目计划通过比较基因组学分析，发掘细胞核基因组中影响细胞器DNA片段插入的特征，探索核基因组本身变小的进化趋势是否是它们接受细胞器DNA的阻力，探索新转移基因获得剪接体内含子的机制，探讨核基因组中转运肽编码序列丰富度是否影响基因成功转移的频率。综合评估现有理论假说的优缺点，提出新假说、完善细胞器基因组进化的理论。本课题的深入研究，不仅可以揭示真核生物遗传系统多样性的进化基础，而且对跨物种水平基因转移、胞质雄性不育、杂种优势、线粒体缺陷的基因治疗等生物、农业、医学难题的解决具有参考价值。

线粒体是真核生物进行有氧代谢获得能量的细胞器，叶绿体是植物和藻类进行光合作用合成有机物释放出氧气的细胞器。这两种细胞器都是由古老的细菌通过内共生方式进入真核细胞演变而来。演变过程中与宿主的关系越来越密切，其中的大部分基因已经转移到细胞核中。但现在二者都保留一定长度的DNA，编码十几个到一两百个基因。之前研究发现，细胞器DNA向细胞核的转移仍在不断发生过程中，很多生物的细胞核基因组中均检测到一定数量的细胞器DNA片段。本项目系统地研究了影响细胞器DNA向细胞核转移的各种因素。别于前人的研究，本项目采用了系统发育比较方法，排除了方法上造成假阳性的可能。我们发现，细胞核基因组越大，发生的转移越多。细胞核基因组中，基因密度与转移片段的多少成反比。我们还发现细胞器基因组中的可转录区转移到细胞核的可能性更大，说明cDNA参与细胞器DNA向细胞核的转移过程。水平基因转移是原核生物进化的主要驱动力之一。然而在真核生物中水平基因转移是否普遍存在争议很大。一种流行的说法是生物体在脱水干燥时细胞核DNA发生大量双链断裂，这些断裂的修复过程为外源DNA整合进入细胞核基因组提供了窗口。如果是这样，细胞核不仅会获得很多其他物种的DNA片段，更会获得大量的细胞器DNA片段。所以可以用细胞器DNA片段向细胞核的转移情况检验这种观念。我们对几十种经常遭受脱水干燥的物种及其近缘物种的比较，没有发现二者基因组中细胞器DNA片段的含量存在显著差异。由此推翻了干燥为水平基因转移提供机会的流行观念。另外，我们考察了有氧代谢对原核生物基因组核苷酸组成进化的影响、人类转录因子基因的剂量敏感性。这些研究中大部分内容先后发表在本领域的国际学术期刊BMC Evolutionary Biology, Frontiers in Genetics和BMC Genomics上。