Complex Loci in human and mouse genomes.
Complex Loci in human and mouse genomes.
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人类和小鼠基因组中的复杂基因座。
DOI：
10.1371/journal.pgen.0020047
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发表时间：
2006-04
期刊：
影响因子：
4.5
通讯作者：
Lipovich, Leonard
中科院分区：
文献类型：
--
作者：
Engstrom, Par G.;Suzuki, Harukazu;Ninomiya, Noriko;Akalin, Altuna;Sessa, Luca;Lavorgna, Giovanni;Brozzi, Alessandro;Luzi, Lucilla;Tan, Sin Lam;Yang, Liang;Kunarso, Galih;ng, Edwin Lian-Cho Ng;Batalov, Serge;Wahlestedt, Claes;Kai, Chikatoshi;Kawai, Jun;Carninci, Piero;Hayashizaki, Yoshihide;Wells, Christine;Bajic, Vladimir B.;Orlando, Valerio;Reid, James F.;Lenhard, Boris;Lipovich, Leonard
哺乳动物基因组具有比预期数量更多的复杂基因座，其中多个基因通过反义方向的共享转录区和/或通过双向核心启动子偶联。为了确定哺乳动物复杂基因座的发生率、功能意义和进化背景，我们从36，606个小鼠转录单位（TU）中鉴定并表征了5，248个顺式反义对、1，638个双向启动子和1，153条多顺式反义和/或双向启动对的链，沿着6，141个顺式反义对、2，113个双向启动子，和来自42,887个人类TU的1,480条链。在人类和小鼠中，25%的TU存在于顺式-反义对中，其中只有17%在两种生物体之间是保守的，表明反义基因排列的频繁种属特异性。抽样方法表明，超过40%的所有TU实际上可能是顺式反义对，只有少数这些安排可能是保守的人和小鼠之间。双向启动子的特征在于可变的转录起始位点和可识别的中点，在该中点处，整体序列组成改变链和转录起始方向切换。在覆盖广泛的小鼠组织的微阵列数据中，顺式-反义和双向促进排列的基因显示出比随机基因对更高的协同表达概率。在同源异型基因座的案例研究中，我们观察到广泛的非编码链上的非保守序列的转录，这意味着这些转录本的存在，而不是序列是功能的重要性。复杂基因座是普遍存在的，宿主众多的非保守基因结构和谱系特异性外显子化事件，并可能对成员基因具有顺式调控作用。在传统观点中，大多数基因在哺乳动物基因组中占据自己独特的领地。然而，很明显，许多基因实际上位于复杂区域（复杂基因座），在那里它们通过利用相反的DNA链与其他基因共享领土。这些基因或者共享表达为mRNA的区域（即，形成顺式-反义对）或从基因组区域（称为双向启动子）开始，在该基因组区域处，转录可以沿DNA以沿着两个方向起始。在本文中，研究人员提出了迄今为止最全面的复杂基因座普查之一，并研究了它们的一般特性和人-鼠差异，以发现这种类型的基因组织的规则及其对基因调控的影响。他们发现大约25%的已知人类和小鼠基因是顺式反义对，估计总比例超过40%。在双向启动子中，他们证明了与启动子在两个方向上启动转录的能力相关的镜像DNA序列组成的存在。研究人员发现了超过2,000个“链”-复杂的排列，其中三个或更多个基因通过顺式-反义配对和/或双向启动子偶联;其中许多基因的产物控制其他基因的表达。
Mammalian genomes harbor a larger than expected number of complex loci, in which multiple genes are coupled by shared transcribed regions in antisense orientation and/or by bidirectional core promoters. To determine the incidence, functional significance, and evolutionary context of mammalian complex loci, we identified and characterized 5,248 cis–antisense pairs, 1,638 bidirectional promoters, and 1,153 chains of multiple cis–antisense and/or bidirectionally promoted pairs from 36,606 mouse transcriptional units (TUs), along with 6,141 cis–antisense pairs, 2,113 bidirectional promoters, and 1,480 chains from 42,887 human TUs. In both human and mouse, 25% of TUs resided in cis–antisense pairs, only 17% of which were conserved between the two organisms, indicating frequent species specificity of antisense gene arrangements. A sampling approach indicated that over 40% of all TUs might actually be in cis–antisense pairs, and that only a minority of these arrangements are likely to be conserved between human and mouse. Bidirectional promoters were characterized by variable transcriptional start sites and an identifiable midpoint at which overall sequence composition changed strand and the direction of transcriptional initiation switched. In microarray data covering a wide range of mouse tissues, genes in cis–antisense and bidirectionally promoted arrangement showed a higher probability of being coordinately expressed than random pairs of genes. In a case study on homeotic loci, we observed extensive transcription of nonconserved sequences on the noncoding strand, implying that the presence rather than the sequence of these transcripts is of functional importance. Complex loci are ubiquitous, host numerous nonconserved gene structures and lineage-specific exonification events, and may have a cis-regulatory impact on the member genes. In the traditional view, most genes occupy their own distinct territory in mammalian genomes. However, it has become apparent that many genes are in fact located in complex regions (complex loci) where they share territory with other genes by utilizing opposite strands of DNA. Such genes either share regions expressed as mRNA (i.e., form cis–antisense pairs) or start from a genome region (called a bidirectional promoter) at which transcription can initiate in both directions along the DNA. In this paper, researchers present the one of the most comprehensive censuses of complex loci to date and investigate their general properties and human–mouse differences to discover the rules of this type of gene organization and its effect on gene regulation. They found about 25% of known human and mouse genes to be in cis–antisense pairs, and estimate the total fraction to be over 40%. At bidirectional promoters, they demonstrated the existence of mirror DNA sequence composition related to the promoters' ability to initiate transcription in two directions. The researchers found over 2,000 “chains”—complex arrangements where three or more genes are coupled by cis–antisense pairing and/or bidirectional promoters; among them are many genes whose products control the expression of other genes.
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