Transcription-coupled and splicing-coupled strand asymmetries in eukaryotic genomes

Transcription-coupled and splicing-coupled strand asymmetries in eukaryotic genomes
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DOI:
10.1093/nar/gkh823
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发表时间:
2004-01-01
影响因子:
14.9
通讯作者:
Thermes, C
Thermes, C
中科院分区:
生物学2区
文献类型:
--
作者:
Touchon, M;Arneodo, A;Thermes, C

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在无链偏置条件下,每条基因组DNA链应该呈现A和T以及G和c的等量性。偏离这些规则归因于DNA突变修复过程固有的不对称特性。在细菌中,链偏倚与复制或转录有关。在真核生物中,最近的研究表明,人类基因存在转录偶联偏差,这可能反映了转录偶联修复过程。在这里,我们研究了进化距离较远的真核生物内含子序列中的链不对称,并表明可以区分两个重叠的内含子偏置。(i)偏差在内含子末端最大,在内部区域随着距离的增加而减小至零,这可能反映了mrna前体和剪接机制之间的相互作用;在哺乳动物和拟南芥中,这些基因长度约为0.5 kb,在秀丽隐杆线虫和黑腹果蝇中,这些基因长度约为1 kb。(ii)沿内含子恒定的偏倚,可能与转录有关。引人注目的是,在秀丽隐杆线虫中,后一种偏见延伸到基因间区域,这些区域分离了共同取向的基因。当适当检查时,所有基因组在编码链上都存在转录偶联的T超过A。相反,GC偏度要么为正(哺乳动物、植物),要么为负(无脊椎动物)。这些结果表明,转录偶联不对称是由脊椎动物和无脊椎动物之间不同的突变修复机制引起的。
Under no-strand bias conditions, each genomic DNA strand should present equimolarities of A and T and of G and C. Deviations from these rules are attributed to asymmetric properties intrinsic to DNA mutation-repair processes. In bacteria, strand biases are associated with replication or transcription. In eukaryotes, recent studies demonstrate that human genes present transcription-coupled biases that might reflect transcription-coupled repair processes. Here, we study strand asymmetries in intron sequences of evolutionarily distant eukaryotes, and show that two superimposed intron biases can be distinguished. (i) Biases that are maximum at intron extremities and decrease over large distances to zero values in internal regions, possibly reflecting interactions between pre-mRNA and splicing machinery; these extend over similar to0.5 kb in mammals and Arabidopsis thaliana, and over 1 kb in Caenorhabditis elegans and Drosophila melanogaster. (ii) Biases that are constant along introns, possibly associated with transcription. Strikingly, in C.elegans, these latter biases extend over intergenic regions that separate co-oriented genes. When appropriately examined, all genomes present transcription-coupled excess of T over A in the coding strand. On the opposite, GC skews are either positive (mammals, plants) or negative (invertebrates). These results suggest that transcription-coupled asymmetries result from mutation-repair mechanisms that differ between vertebrates and invertebrates.