重复基因的进化一回顾与进展

基因重复是普遍存在的生物学现象, 是基因组和遗传系统多样化的重要推动力量, 在生物进化过程中发挥着极其重要的作用。基因重复有何利弊, 基因发生重复后, 2个重复子拷贝的保留在基因功能方面是否存在偏好性, 子拷贝在表达和进化速率上如何分化, 以及重复基因为什么会被保留下来一直是进化生物学领域研究的热点问题之一。该文对以上重复基因研究的热点问题进行了介绍, 并对重复基因的进化机制和理论模型及其近年来的一些主要研究进展进行了综述。     

功能基因中的微卫星序列

微卫星序列广泛存在真核生物和一些原核生物的基因组中,它在基因组中的分布并不是随机的。不同重复拷贝类别在基因组中存在种属间和碱基组成的特异性,各种优势的重复序列类型不同。此外,基因中在编码区和非编码区的分布也表现出种属和碱基组成差异。这种差异显示了微卫星序列起源进化的复杂性,也反映了基因中微卫星序列的生物学功能。功能基因为遗传学工作者提供了一个联系表型和基因型的手段,研究功能基因中的微卫星序列不仅在绘制精细遗传图谱、筛选重要农艺性状基因、物种进化等问题上都有着重要的作用,而且在疾病治疗有潜在的应用价值。本文主要阐述了微卫星序列的形成机制、基因中微卫星序列的分布以及功能基因中微卫星序列的生物学作用,并指出了目前实践中的一些问题。     

F-box基因拷贝数目变异的机制研究:以12种果蝇为例

拷贝数目变异是一种对表型变异和生物进化具有重要意义的基因组结构变异.以前的研究表明不同物种中F-box基因的拷贝数目差异较大.为了深入探索拷贝数目变异的式样和机制.我们以12个果蝇近缘种为研究对象,分析了F-box基因的系统发育关系、进化式样以及它们在染色体上的位置.结果发现,虽然各个物种中F-box基因的拷贝数目差别不大(42-47个),但是仍然存在着很多引起拷贝数目变异的基因获得和丢失事件.这说明表面上变化不大的拷贝数目在一定程度上掩盖了频繁发生的基因获得和丢失事件.通过比较这些基因在染色体上的位置,发现只有在亲缘关系很近的物种之间才能鉴定出有明显微共线性关系的基因组区段.我们还发现,造成F-box基因拷贝数目增加的主要机制是散在重复和串联重复,而反转录转座和新基因的非编码区起源也是两种值得注意的机制.此外,序列变异导致的外显子边界变化以及外显子丢失是引起拷贝数目减少的两种机制.在12种果蝇的最近共同祖先中,F-box基因的拷贝数目与现存物种基本相似,但是基因的获得和丢失事件使得现存物种中的F-box基因在构成上已经有了明显的差别.对数目变异的式样及其与基因功能的关系的研究表明,拷贝数目变异是F-box基因家族"生与死"的进化在基因组层面的系统反映,并有可能为表型变异提供了原始材料.     

拟南芥花药绒毡层细胞中具有基因簇特征的基因进化和功能分析

在植物基因组中, 除了同源基因成簇现象外, 近年来还发现一些具有共表达特性的异源基因也能够以基因簇形式存在, 但这些异源基因簇的进化和生物学功能尚不清楚。花药发育和花粉形成是植物进化出的特有的生殖生物学过程, 同时产生了一些在花药绒毡层中特异表达和特定功能的基因簇基因。该研究通过筛选和分析花药绒毡层中基因簇基因的分子特性、表达调控、基因年龄和基因重复进化等信息, 探讨花药基因簇基因与植物开花功能进化之间的关系。结果表明, 在拟南芥(Arabidopsis thaliana)中共筛选到84个(13个基因簇)花药绒毡层特异高表达的基因簇基因, 它们主要产生于串联重复事件, 76%的基因出现在开花植物分化后的阶段, 主要参与生殖发育、花粉鞘组成和脂代谢等生物学过程。研究初步解析了拟南芥花药绒毡层中基因簇基因的基本特征、生物学功能和基因进化机制, 为深入揭示植物基因簇基因的遗传学功能奠定了基础。     

拟南芥花药绒毡层细胞中具有基因簇特征的基因进化和功能分析

在植物基因组中,除了同源基因成簇现象外,近年来还发现一些具有共表达特性的异源基因也能够以基因簇形式存在,但这些异源基因簇的进化和生物学功能尚不清楚。花药发育和花粉形成是植物进化出的特有的生殖生物学过程,同时产生了一些在花药绒毡层中特异表达和特定功能的基因簇基因。该研究通过筛选和分析花药绒毡层中基因簇基因的分子特性、表达调控、基因年龄和基因重复进化等信息,探讨花药基因簇基因与植物开花功能进化之间的关系。结果表明,在拟南芥(Arabidopsisthaliana)中共筛选到84个(13个基因簇)花药绒毡层特异高表达的基因簇基因,它们主要产生于串联重复事件,76%的基因出现在开花植物分化后的阶段,主要参与生殖发育、花粉鞘组成和脂代谢等生物学过程。研究初步解析了拟南芥花药绒毡层中基因簇基因的基本特征、生物学功能和基因进化机制,为深入揭示植物基因簇基因的遗传学功能奠定了基础。     

拟南芥和琴叶拟南芥中MADS-box基因的比较进化分析

MADS-box基因编码一类转录因子。在被子植物中,MADS-box基因对于营养生长和生殖发育都有重要的调控作用,是植物体(特别是花序、花和果实)的正常发育所不可或缺的。为了理解近缘物种在遗传基础上的异同,我们对拟南芥(Arabidopsis thaliana)和琴叶拟南芥(A.lyrata)基因组中MADS-box基因的拷贝数目和进化式样进行了比较分析。通过搜索公共数据库,我们在拟南芥和琴叶拟南芥中分别鉴定出了106和115个基因。系统发育分析的结果表明,这些基因属于I型和II型MADS-box基因。在两个物种分化之后,II型基因的拷贝数目变化不大,I型基因则经历了多次独立的基因丢失和获得事件。通过比较这些基因在染色体上的排列,我们不但鉴定出了存在微共线性的基因组区段,而且发现新基因产生的主要机制是串联重复和散在重复。分子进化的研究进一步表明,I型和II型基因在进化式样上存在着显著差异:II型基因在进化中一般都受到了较强的选择压力,而I型基因大多受到的选择压力较弱。本研究将为深入理解近缘物种在基因和基因组层面上的异同、探讨物种分化和生物多样性形成的机制等问题提供新思路。     

以发育模块重复征用和整合为基础的进化创新机制

进化新征的起源和分化是进化发育生物学研究的核心问题。通过对多细胞生物早期发育调控机制的比较分析,发现亲缘关系较远的生物所共有的一些形态特征受保守的发育调控程序调节（深同源性）。许多创新性状的发生是基于对预先存在的基因或发育调控模块的重复利用和整合。发育基因调控网络在结构和功能上高度模块化,因此不仅可以通过模块拆分和重复征用改变发育程式,而且也增强了调控网络自身的进化力。研究基因调控网络和发育系统的进化动态将有助于更深入地认识生物演化过程中创新性状发生和表型进化的分子机制。     

木根麦冬与林生麦冬5S rRNA基因的进化

为了揭示多拷贝基因的进化方式,对濒危植物木根麦冬（Ophiopogon xylorrhizus Wang et Dai)3个居群、6个个体的294个5S rRNA基因拷贝及其姐妹种林生麦冬（O.sylvicola Wang et Tang) 的45个拷贝进行了DNA测序和序列分析,并以这个迄今发表的最大的单个物种的5S rDNA基因数据,以PAUP程序重建了分子系统发育树。结果表明：1）所得序列呈高度多样性,长度变化在307－548碱基之间,仅13对（3．8％）相同,序列分化指数较高：木根麦冬是0．078,林生麦冬是0．032,两物种间是0．149;2）100％的统计值支持两物种的5S rRNA基因分别来自于祖先种的一个拷贝,即“建立者拷贝”,这个拷贝在物种形成之后进行了一系列连续的扩增,形成一个直系的基因家族,而祖先种的其他拷贝在物种形成后被丢失;3）不同拷贝是独立进化的,序列间的一致化过程很弱,这在串联重复的rRNA基因中是罕见的;4）木根麦冬居群间曾存在频繁的基因交流,使5S rRNA基因的许多拷贝扩散于不同居群,维持着种内较高的遗传多样性。可以认为是某些近期发生的变化,阻止了居群间的基因交流,导致该物种广泛的自交,发生自交衰退,并最后导致濒危。     

串联重复序列的物种差异及其生物功能

串联重复序列是指1-200个碱基左右的核心重复单位,以头尾相串联的方式重复多次所组成的重 复序列。它广泛存在于真核生物和一些原核生物的基因组中,并表现出种属、碱基组成等的特异性。在基因组 整体水平上,各种优势的重复序列类型不同。即使在同一重复序列类型内部,不同重复拷贝类别(如AT、AC 等)在基因组中的存在也表现出很大的差异。同时,这些重复序列类型和各重复拷贝类别在同一物种的不同染 色体间,以及基因的编码区和非编码区间也表现种属和碱基组成差异。这些差异显示了重复序列起源和进化的 复杂性,可能涉及到多种机制和因素,并与生物功能密切相关。另外,由于重复序列分析软件和统计标准还存 在算法、重复长度、完美性等问题,需要进一步探讨。此外,串联重复序列的自身进化关系、全基因组水平上 的进化地位、在基因组中的生物功能、重复序列数据库建立和应用研究等,将是今后研究的主要课题。     

木根麦冬与林生麦冬5S rRNA基因的进化

为了揭示多拷贝基因的进化方式, 对濒危植物木根麦冬(Ophiopogon xylorrhizus Wang et Dai) 3个居群、6个个体的294个5S rR NA 基因拷贝及其姐妹种林生麦冬(O. sylvicola Wang et Tang)的45个拷贝进行了DNA测序和序列分析,并以这个迄今发表的最大的单个物种的5S rRNA基因数据,以PAUP程序重建了分子系统发育树.结果表明: 1)所得序列呈高度多样性,长度变化在307～548碱基之间,仅13对(3.8%)相同,序列分化指数较高:木根麦冬是0.078,林生麦冬是0.032,两物种间是0.149; 2)100%的统计值支持两物种的5S rRNA 基因分别来自于祖先种的一个拷贝,即"建立者拷贝",这个拷贝在物种形成之后进行了一系列连续的扩增,形成一个直系的基因家族,而祖先种的其他拷贝在物种形成后被丢失; 3)不同拷贝是独立进化的,序列间的一致化过程很弱,这在串联重复的rR N A基因中是罕见的; 4)木根麦冬居群间曾存在频繁的基因交流,使5S rRNA 基因的许多拷贝扩散于不同居群,维持着种内较高的遗传多样性.可以认为是某些近期发生的变化,阻止了居群间的基因交流,导致该物种广泛的自交,发生自交衰退,并最后导致濒危.     

基因倍增研究进展

基因倍增是指DNA片段在基因组中复制出一个或更多的拷贝,这种DNA片段可以是一小段基因组序列、整条染色体,甚至是整个基因组。基因倍增是基因组进化最主要的驱动力之一,是产生具有新功能的基因和进化出新物种的主要原因之一。本文综述了脊椎动物、模式植物和酵母在进化过程中基因倍增研究领域的最新进展,并讨论了基因倍增研究的发展方向。     

Significantly different patterns of amino acid replacement after gene duplication as compared to after speciation

We have performed a large-scale analysis of amino acid sequence evolution after gene duplication by comparing evolution after gene duplication with evolution after speciation in over 1,800 phylogenetic trees constructed from manually curated alignments of protein domains downloaded from the PFAM database. The site-specific rate of evolution is significantly altered by gene duplication. A significant increase in the proportion of amino acid substitutions at constrained (slowly evolving) sites after duplication was observed. An increase in the proportion of replacements at normally constrained amino acid sites could result from relaxation of purifying selective pressure. However, the proportion of amino acid replacements involving radical changes in amino acid properties after duplication does not appear to be significantly increased by relaxed selective pressure. The increased proportion of replacements at constrained sites was observed over a relatively large range of protein change (up to 25% amino acid replacements per site). These findings have implications for our understanding of the nature of evolution after duplication and may help to shed light on the evolution of novel protein functions through gene duplication.     

Role of gene duplication in evolution

It is now known that many multigene and supergene families exist in eukaryote genomes: multigene families with uniform copy members like genes for ribosomal RNA, those with variable members like immunoglobulin genes, and supergene families such as those for various growth factor and hormone receptors. Many such examples indicate that gene duplication and subsequent differentiation are extremely important for organismal evolution. In particular, gene duplication could well have been the primary mechanism for the evolution of complexity in higher organisms. Population genetic models for the origin of gene families with diverse functions are presented, in which natural selection favors those genomes with more useful mutants in duplicated genes. Since any gene has a certain probability of degenerating by mutation, success versus failure in acquiring a new gene by duplication may be expressed as the ratio of probabilities of spreading of useful versus detrimental mutations in redundant gene copies. Also examined are the effects of gene duplication on evolution by compensatory advantageous mutations. Results of the analyses show that both natural selection and random drift are important for the origin of gene families. In addition, interaction between molecular mechanisms such as unequal crossing-over and gene conversion, and selection or drift is found to have a large effect on evolution by gene duplication.     

Gene duplication and the evolution of phenotypic diversity in insect societies

Gene duplication is an important evolutionary process thought to facilitate the evolution of phenotypic diversity. We investigated if gene duplication was associated with the evolution of phenotypic differences in a highly social insect, the honeybee Apis mellifera. We hypothesized that the genetic redundancy provided by gene duplication could promote the evolution of social and sexual phenotypes associated with advanced societies. We found a positive correlation between sociality and rate of gene duplications across the Apoidea, indicating that gene duplication may be associated with sociality. We also discovered that genes showing biased expression between A. mellifera alternative phenotypes tended to be found more frequently than expected among duplicated genes than singletons. Moreover, duplicated genes had higher levels of caste‐, sex‐, behavior‐, and tissue‐biased expression compared to singletons, as expected if gene duplication facilitated phenotypic differentiation. We also found that duplicated genes were maintained in the A. mellifera genome through the processes of conservation, neofunctionalization, and specialization, but not subfunctionalization. Overall, we conclude that gene duplication may have facilitated the evolution of social and sexual phenotypes, as well as tissue differentiation. Thus this study further supports the idea that gene duplication allows species to evolve an increased range of phenotypic diversity.     

Processes of fungal proteome evolution and gain of function: gene duplication and domain rearrangement

During evolution, organisms have gained functional complexity mainly by modifying and improving existing functioning systems rather than creating new ones ab initio. Here we explore the interplay between two processes which during evolution have had major roles in the acquisition of new functions: gene duplication and protein domain rearrangements. We consider four possible evolutionary scenarios: gene families that have undergone none of these event types; only gene duplication; only domain rearrangement, or both events. We characterize each of the four evolutionary scenarios by functional attributes. Our analysis of ten fungal genomes indicates that at least for the fungi clade, species significantly appear to gain complexity by gene duplication accompanied by the expansion of existing domain architectures via rearrangements. We show that paralogs gaining new domain architectures via duplication tend to adopt new functions compared to paralogs that preserve their domain architectures. We conclude that evolution of protein families through gene duplication and domain rearrangement is correlated with their functional properties. We suggest that in general, new functions are acquired via the integration of gene duplication and domain rearrangements rather than each process acting independently.     

Mass-murder deletion of 19 ORFs from Saccharomyces cerevisiae chromosome XI

In eukaryote genomes, there are many kinds of gene families. Gene duplication and conversion are sources of the evolution of gene families, including those with uniform members and those with diverse functions. Population genetics theory on identity coefficients among gene members of a gene family shows that the balance between diversification by mutation, and homogenization by unequal crossing over and gene conversion, is important. Also, evolution of new functions is due to gene duplication followed by differentiation. Positive selection is necessary for the evolution of novel functions. However, many examples of current gene families suggest that both drift and selection are at work on their evolution.     

基因重复研究进展

基因复制是基因通过不等交换,反转录转座或由全基因组复制等途径产生一个与原基因相似的基因或碱基序列,它与生物体基因组大小的进化、新基因的起源、物种的分化以及基因抗突变的能力大小等都密切相关。本文综述了复制基因的产生和保留机制、选择作用、分化的途径以及复制基因进化速率等方面的相关研究,揭示了基因复制对于生物进化的重要性,以引起大家对该领域的了解与关注。关键词：基因复制;复制基因;不等交换;反转录转座;全基因组复制     

Pyrrolizidine alkaloid biosynthesis,evolution of a pathway in plant secondary metabolism

The system of pyrrolizidine alkaloids has proven to be a powerful system for studying the evolution of a biosynthetic pathway in plant secondary metabolism. Pyrrolizidine alkaloids are typical plant secondary products produced by the plant as a defense against herbivores. The first specific enzyme, homospermidine synthase, has been shown to have evolved by duplication of the gene encoding deoxyhypusine synthase, which is involved in primary metabolism. Despite the identical function of homospermidine synthase for pyrrolizidine alkaloid biosynthesis in the various plant lineages, this gene duplication has occurred several times independently during angiosperm evolution. After duplication, these gene copies diverged with respect to gene function and regulation. In the diverse plant lineages producing pyrrolizidine alkaloids, homospermidine synthase has been shown to be expressed in a variety of tissues, suggesting that the regulatory elements were recruited individually after the duplication of the structural gene. The molecular, kinetic, and expression data of this system are discussed with respect to current models of gene and pathway evolution.     

Molecular Evidence for Asymmetric Evolution of Sister Duplicated Blocks after Cereal Polyploidy

Polyploidy (genome duplication) is thought to have contributed to the evolution of the eukaryotic genome, but complex genome structures and massive gene loss during evolution has complicated detection of these ancestral duplication events. The major factors determining the fate of duplicated genes are currently unclear, as are the processes by which duplicated genes evolve after polyploidy. Fine-scale analysis between homologous regions may allow us to better understand post-polyploidy evolution. Here, using gene-by-gene and gene-by-genome strategies, we identified the S5 region and four homologous regions within the japonica genome. Additional phylogenomic analyses of the comparable duplicated blocks indicate that four successive duplication events gave rise to these five regions, allowing us to propose a model for this local chromosomal evolution. According to this model, gene loss may play a major role in post-duplication genetic evolution at the segmental level. Moreover, we found molecular evidence that one of the sister duplicated blocks experienced more gene loss and a more rapid evolution subsequent to two recent duplication events. Given that these two recent duplication events were likely involved in polyploidy, this asymmetric evolution (gene loss and gene divergence) may be one possible mechanism accounting for the diploidization at the segmental level. Supplementary material to this paper is available in electronic form at http://dx.doi.org/10.1007/s11103-005-4414-1