Strand compositional asymmetries of nuclear DNA in eukaryotes

Strand compositional asymmetries of nuclear DNA in eukaryotes
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DOI:
10.1007/s00239-003-2483-9
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发表时间:
2003-09-01
影响因子:
3.9
通讯作者:
Zhang, DY
Zhang, DY
中科院分区:
生物学3区
文献类型:
--
作者:
Niu, DK;Lin, K;Zhang, DY

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DNA复制和转录都是结构上不对称的过程。在真细菌、病毒和细胞器基因组中,前导链和滞后链之间、编码链和非编码链之间存在不对称的核苷酸取代模式。在真核生物中类似的研究很少,因为核基因组复制的起源大多是未知的,而且复制子比原核生物的复制子短得多。为了避免这些困境,我们从酿酒酵母、pombe Schizosaccharomyces、恶性疟原虫、cucuuli脑囊虫、拟南芥、秀丽隐杆线虫、黑腹果蝇、冈比亚按蚊、小家鼠和智人的全基因组中选择了所有可能位于不同核DNA链上的邻近基因对。对于这样一对基因,一个可能由前导链编码,另一个可能由后导链编码。通过检查每对基因中的内含子和密码子的四重简并位点,我们发现在大多数真核生物中,T与A和G与C的相对频率明显偏斜。在基因对中,复制和转录相关的突变偏差对链不对称的潜在影响在一个基因中是相同方向的,其中前导链合成与转录共享相同的模板,而它们在另一个基因中往往被抵消。我们的研究表明,DNA复制相关和转录相关的突变偏倚和/或选择性密码子使用偏倚可能不对称地影响真核生物基因组的链核苷酸组成。
Both DNA replication and transcription are structurally asymmetric processes. An asymmetric nucleotide substitution pattern has been observed between the leading and the lagging strand, and between the coding and the noncoding strand, in eubacterial, viral, and organelle genomes. Similar studies in eukaryotes have been rare, because the origins of replication in nuclear genomes are mostly unknown and the replicons are much shorter than those of prokaryotes. To circumvent these predicaments, all possible pairs of neighboring genes that are located on different strands of nuclear DNA were selected from the complete genomes of Saccharomyces cerevisiae, Schizosaccharomyces pombe, Plasmodium falciparum, Encephalitozoon cuniculi, Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster, Anopheles gambiae, Mus musculus, and Homo sapiens. For such a pair of genes, one is likely coded from the leading strand and the other from the lagging strand. By examining the introns and the fourfold degenerate sites of codons in the genes of each pair, we found that the relative frequencies of T vs. A and of G vs. C are significantly skewed in most eukaryotes studied. In a gene pair, the potential effects of replication- and transcription-associated mutation bias on strand asymmetry are in the same direction for one gene where leading strand synthesis shares the same template with transcription, while they tend to be canceled out in the other gene. Our study demonstrates that DNA replication-associated and transcription-associated mutation bias and/or selective codon usage bias may affect the strand nucleotide composition asymmetrically in eukaryotic genomes.