Santini Simona, Boore Jeffrey L, Meyer Axel
Department of Biology, University of Konstanz, 78457 Konstanz, Germany.
Genome Res. 2003 Jun;13(6A):1111-22. doi: 10.1101/gr.700503.
Comparisons of DNA sequences among evolutionarily distantly related genomes permit identification of conserved functional regions in noncoding DNA. Hox genes are highly conserved in vertebrates, occur in clusters, and are uninterrupted by other genes. We aligned (PipMaker) the nucleotide sequences of the HoxA clusters of tilapia, pufferfish, striped bass, zebrafish, horn shark, human, and mouse, which are separated by approximately 500 million years of evolution. In support of our approach, several identified putative regulatory elements known to regulate the expression of Hox genes were recovered. The majority of the newly identified putative regulatory elements contain short fragments that are almost completely conserved and are identical to known binding sites for regulatory proteins (Transfac database). The regulatory intergenic regions located between the genes that are expressed most anteriorly in the embryo are longer and apparently more evolutionarily conserved than those at the other end of Hox clusters. Different presumed regulatory sequences are retained in either the Aalpha or Abeta duplicated Hox clusters in the fish lineages. This suggests that the conserved elements are involved in different gene regulatory networks and supports the duplication-deletion-complementation model of functional divergence of duplicated genes.
对进化上远缘相关基因组之间的DNA序列进行比较，有助于识别非编码DNA中的保守功能区域。Hox基因在脊椎动物中高度保守，成簇存在，且不被其他基因打断。我们（使用PipMaker）比对了罗非鱼、河豚、条纹鲈、斑马鱼、角鲨、人类和小鼠的HoxA簇的核苷酸序列，这些物种在进化上相隔约5亿年。作为对我们方法的支持，一些已知调控Hox基因表达的假定调控元件被识别出来。大多数新识别出的假定调控元件包含几乎完全保守的短片段，并且与调控蛋白的已知结合位点（转录因子数据库）相同。位于胚胎中最前端表达的基因之间的调控基因间区域比Hox簇另一端的区域更长，且在进化上明显更保守。在鱼类谱系中，不同的假定调控序列保留在Aα或Aβ重复的Hox簇中。这表明保守元件参与了不同的基因调控网络，并支持了重复基因功能分化的复制-缺失-互补模型。
