Engström Pär 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-Chong, 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
Computational Biology Unit, Bergen Center for Computational Science, University of Bergen, Bergen, Norway.
PLoS Genet. 2006 Apr;2(4):e47. doi: 10.1371/journal.pgen.0020047. Epub 2006 Apr 28.
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.
哺乳动物基因组中复杂基因座的数量超出预期，在这些基因座中，多个基因通过反义方向的共享转录区域和/或双向核心启动子相互关联。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个小鼠转录单元（TU）中鉴定并表征了5,248个顺式反义对、1,638个双向启动子以及1,153个由多个顺式反义对和/或双向促进对组成的链，同时从42,887个人类TU中鉴定并表征了6,141个顺式反义对、2,113个双向启动子以及1,480个链。在人类和小鼠中，25%的TU存在于顺式反义对中，其中只有17%在两种生物之间保守，这表明反义基因排列具有频繁的物种特异性。一种抽样方法表明，所有TU中超过40%实际上可能处于顺式反义对中，而且这些排列中只有少数可能在人类和小鼠之间保守。双向启动子的特征是转录起始位点可变，并且有一个可识别的中点，在该中点处整体序列组成在链上发生变化，转录起始方向也发生切换。在涵盖多种小鼠组织的微阵列数据中，处于顺式反义排列和双向促进排列的基因比随机配对的基因更有可能协同表达。在一个关于同源异型基因座的案例研究中，我们观察到非编码链上非保守序列的广泛转录，这意味着这些转录本的存在而非序列具有功能重要性。复杂基因座无处不在，包含众多非保守基因结构和谱系特异性外显子化事件，并且可能对成员基因产生顺式调控影响。
