The regulatory content of intergenic DNA shapes genome architecture.

The regulatory content of intergenic DNA shapes genome architecture.
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DOI:
10.1186/gb-2004-5-4-r25
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发表时间:
2004
期刊:
影响因子:
12.3
通讯作者:
Carroll SB
Carroll SB
中科院分区:
生物学1区
文献类型:
--
作者:
Nelson CE;Hersh BM;Carroll SB

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研究了秀丽隐杆线虫和黑腹果蝇调控复杂性与基因间距的关系。基因间距离和基因组结构是由非编码DNA中包含的调控信息决定的。影响后生动物基因组中功能不相关基因的组织和间距的因素尚不清楚。由于与已知的调节区和蛋白质编码区相比,典型的后生动物基因组的大小很大,因此通常认为功能DNA对基因间距和基因组组织的影响可以忽略不计。特别是,要估计调控元件对基因组结构的全球影响(如果有的话)是不可能的。为了研究这一点,我们研究了秀丽隐杆线虫和黑腹果蝇的调控复杂性和基因间距之间的关系。我们发现基因密度直接反映了局部调控复杂性,因此基因与其最近邻居之间的非编码DNA的数量与该基因的调控复杂性呈正相关。具有复杂功能的基因比具有简单或管家功能的基因有更多的非编码DNA。在黑腹线虫和秀丽隐杆线虫中,低调控复杂性的基因与大约相同数量的非编码DNA相关,而在更复杂的动物中,高调控复杂性的基因座明显更大。秀丽隐杆线虫的复杂基因具有大于5′的非编码间隔,而黑腹线虫的复杂基因具有大致相等的5′和3′非编码间隔。基因间距离,因此基因组结构,是高度非随机的。相反,它是由包含在非编码DNA中的调控信息形成的。我们的研究结果表明,在紧凑型基因组中,非功能性DNA的物种特异性缺失通过在其尾迹中留下功能性DNA的轮廓,揭示了调控信息的景观。
The relationship between regulatory complexity and gene spacing was examined in Caenorhabditis elegans and Drosophila melanogaster. Intergenic distance, and hence genome architecture, is shaped by regulatory information contained in noncoding DNA. Factors affecting the organization and spacing of functionally unrelated genes in metazoan genomes are not well understood. Because of the vast size of a typical metazoan genome compared to known regulatory and protein-coding regions, functional DNA is generally considered to have a negligible impact on gene spacing and genome organization. In particular, it has been impossible to estimate the global impact, if any, of regulatory elements on genome architecture. To investigate this, we examined the relationship between regulatory complexity and gene spacing in Caenorhabditis elegans and Drosophila melanogaster. We found that gene density directly reflects local regulatory complexity, such that the amount of noncoding DNA between a gene and its nearest neighbors correlates positively with that gene's regulatory complexity. Genes with complex functions are flanked by significantly more noncoding DNA than genes with simple or housekeeping functions. Genes of low regulatory complexity are associated with approximately the same amount of noncoding DNA in D. melanogaster and C. elegans, while loci of high regulatory complexity are significantly larger in the more complex animal. Complex genes in C. elegans have larger 5' than 3' noncoding intervals, whereas those in D. melanogaster have roughly equivalent 5' and 3' noncoding intervals. Intergenic distance, and hence genome architecture, is highly nonrandom. Rather, it is shaped by regulatory information contained in noncoding DNA. Our findings suggest that in compact genomes, the species-specific loss of nonfunctional DNA reveals a landscape of regulatory information by leaving a profile of functional DNA in its wake.
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