Extreme conservation of noncoding DNA near HoxD complex of vertebrates -: art. no. 75
Extreme conservation of noncoding DNA near HoxD complex of vertebrates -: art. no. 75
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DOI：
10.1186/1471-2164-5-75
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发表时间：
2004-10-06
期刊：
影响因子：
4.4
通讯作者：
Mishra, RK
中科院分区：
文献类型：
--
作者：
Sabarinadh, C;Subramanian, S;Mishra, RK
背景：同源异型基因复合体决定动物的前后体轴。hox基因沿着该轴的表达模式和功能与它们在复合体中的组织顺序共线。这种“染色体组织和功能对应”在所有研究的双侧性动物中是保守的。现在已经有了几种脊椎动物的HoxD复合体的基因组序列。这提供了一个比较基因组学的方法，以确定保守的区域连接到这个复杂的。虽然“共线性”的Hox复合物的分子基础还不清楚，它是可能的，有控制元件内或在这些复合物的附近，建立和维持的表达模式的Hox基因在一个协调的fashion.Results：我们比较了DNA序列侧翼的HoxD复合物的几种灵长类动物，啮齿动物和鱼类。该分析揭示了从鱼类到人类的HoxD复合物附近的非编码DNA序列的前所未有的保守性。HoxD复合物上游7 kb区域中数百个碱基对的延伸在脊椎动物物种中显示100%的保守性。使用来自人类序列的PCR引物，这些保守区域可以从其他脊椎动物物种，包括其他哺乳动物、鸟类、爬行动物、两栖动物和鱼类中扩增。我们对这些序列的分析还表明，从保守的核心区域开始，更多的序列已经添加并保持从鱼类到人类的进化过程中。结论：在这种7kb的DNA的核心区域，在类似5亿年的进化中没有发生变化，这种高度的保守性，表明这些序列的关键功能。我们认为，这样的序列很可能提供分子把手，以了解相关基因复合物的进化和调控机制。
Background: Homeotic gene complexes determine the anterior-posterior body axis in animals. The expression pattern and function of hox genes along this axis is colinear with the order in which they are organized in the complex. This 'chromosomal organization and functional correspondence' is conserved in all bilaterians investigated. Genomic sequences covering the HoxD complex from several vertebrate species are now available. This offers a comparative genomics approach to identify conserved regions linked to this complex. Although the molecular basis of 'colinearity' of Hox complexes is not yet understood, it is possible that there are control elements within or in the proximity of these complexes that establish and maintain the expression patterns of hox genes in a coordinated fashion.Results: We have compared DNA sequence flanking the HoxD complex of several primate, rodent and fish species. This analysis revealed an unprecedented conservation of non-coding DNA sequences adjacent to the HoxD complex from fish to human. Stretches of hundreds of base pairs in a 7 kb region, upstream of HoxD complex, show 100% conservation across the vertebrate species. Using PCR primers from the human sequence, these conserved regions could be amplified from other vertebrate species, including other mammals, birds, reptiles, amphibians and fish. Our analysis of these sequences also indicates that starting from the conserved core regions, more sequences have been added on and maintained during evolution from fish to human.Conclusion: Such a high degree of conservation in the core regions of this 7 kb DNA, where no variation occurred during similar to500 million years of evolution, suggests critical function for these sequences. We suggest that such sequences are likely to provide molecular handle to gain insight into the evolution and mechanism of regulation of associated gene complexes.