Early evolution of conserved regulatory sequences associated with development in vertebrates.
Early evolution of conserved regulatory sequences associated with development in vertebrates.
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DOI：
10.1371/journal.pgen.1000762
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发表时间：
2009-12
期刊：
影响因子：
4.5
通讯作者：
Elgar G
中科院分区：
文献类型：
--
作者：
McEwen GK;Goode DK;Parker HJ;Woolfe A;Callaway H;Elgar G
不同脊椎动物基因组之间的比较已经发现了数千个高度保守的非编码序列，其中越来越多的序列已被证明在早期发育过程中起增强子的作用。尽管从人类到软骨鱼类，这些元素在5亿多年的时间里一直处于极端保守状态，但这些元素似乎在无脊椎动物中基本上不存在，而且迄今为止，人们对它们的作用模式或模拟它们的进化过程知之甚少。我们现在已经利用了新兴的基因组序列数据的海七鳃鳗，Petromyzon marinus，探索这种类型的元素在最早的分歧现存的脊椎动物谱系，无颌鱼（agnathans）的保护深度。我们在13个人类基因位点搜索保守的非编码元件（CNEs），并确定七鳃鳗元件与所有这些基因区域，但两个。虽然显着较短，不太保守，比有颌脊椎动物，确定七鳃鳗CNE能够驱动特定模式的表达在斑马鱼胚胎，这是几乎相同的驱动相当于人类元素。因此，这些CNE是所有脊椎动物的独特和定义特征。此外，七鳃鳗和其他脊椎动物CNEs的对齐应允许识别负责共同表达模式的持久序列签名，并有助于阐明CNEs中的监管语言。确定所有脊椎动物共同的发育核心调控密码，为构建调控网络提供了基础，也可能阐明大的保守调控序列块如何进化并固定在基因组DNA中。最近的脊椎动物基因组的比较分析，导致在协调早期发展的基因附近的高度保守的非编码序列的鉴定。这些序列中的许多可以激活基因表达，并且被认为是重要的调控元件。令人惊讶的是，在包括鲨鱼在内的每一种有颌脊椎动物中都发现了大量这些长而几乎相同的序列，但在非脊椎动物中几乎完全不存在。这项研究在七鳃鳗中寻找这组序列，七鳃鳗是我们最远的脊椎动物亲属的代表，以确定何时以及如何在基因组中建立这样一组重要的非编码调控序列。虽然七鳃鳗的分歧只是比软骨鱼类（包括鲨鱼）的分歧稍早，但相对较少，而且相当短，保守的非编码序列是可识别的。然而，这些较短的七鳃鳗序列能够以与人类相同的方式在斑马鱼胚胎中以精确的空间模式驱动基因表达。这一分析揭示了这些调控序列的出现在早期脊椎动物进化过程中，在全基因组复制和相当大的形态变异的时候，与这些序列在指导脊椎动物发育的基因调控网络中的作用一致。
Comparisons between diverse vertebrate genomes have uncovered thousands of highly conserved non-coding sequences, an increasing number of which have been shown to function as enhancers during early development. Despite their extreme conservation over 500 million years from humans to cartilaginous fish, these elements appear to be largely absent in invertebrates, and, to date, there has been little understanding of their mode of action or the evolutionary processes that have modelled them. We have now exploited emerging genomic sequence data for the sea lamprey, Petromyzon marinus, to explore the depth of conservation of this type of element in the earliest diverging extant vertebrate lineage, the jawless fish (agnathans). We searched for conserved non-coding elements (CNEs) at 13 human gene loci and identified lamprey elements associated with all but two of these gene regions. Although markedly shorter and less well conserved than within jawed vertebrates, identified lamprey CNEs are able to drive specific patterns of expression in zebrafish embryos, which are almost identical to those driven by the equivalent human elements. These CNEs are therefore a unique and defining characteristic of all vertebrates. Furthermore, alignment of lamprey and other vertebrate CNEs should permit the identification of persistent sequence signatures that are responsible for common patterns of expression and contribute to the elucidation of the regulatory language in CNEs. Identifying the core regulatory code for development, common to all vertebrates, provides a foundation upon which regulatory networks can be constructed and might also illuminate how large conserved regulatory sequence blocks evolve and become fixed in genomic DNA. Recent comparative analyses of vertebrate genomes has resulted in the identification of highly conserved non-coding sequences near genes that coordinate early development. Many of these sequences can activate gene expression and are thought to be important regulatory elements. Surprisingly, a large set of these long, near-identical sequences is found in every jawed vertebrate, including sharks, yet almost completely absent in non-vertebrates. This study looks for this set of sequences in the lamprey, a representative of our most distant vertebrate relatives, in order to determine when and how such a large set of important non-coding regulatory sequences became established in the genome. Although the lamprey divergence is only a little older than the divergence of cartilaginous fish (including sharks), relatively few, and considerably shorter, conserved non-coding sequences are identifiable. Nevertheless, these shorter lamprey sequences are capable of driving gene expression in a precise spatial pattern in zebrafish embryos in the same way as the equivalent human elements. This analysis has shed light on the emergence of these regulatory sequences during early vertebrate evolution, at a time of whole-genome duplications and considerable morphological variation, consistent with a role for these sequences in directing gene regulatory networks for vertebrate development.
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影响因子：
3.5
作者：
McCauley, DW;Bronner-Fraser, M
通讯作者：
Bronner-Fraser, M
影响因子：
4.6
作者：
Jeong, YS;El-Jaick, K;Epstein, DJ
通讯作者：
Epstein, DJ
DOI：
10.1002/jez.b.00037
发表时间：
2003-10-15
影响因子：
2.2
作者：
Fried, C;Prohaska, SJ;Stadler, PF
通讯作者：
Stadler, PF
影响因子：
64.8
作者：
Delsuc, F;Brinkmann, H;Philippe, H
通讯作者：
Philippe, H
影响因子：
56.9
作者：
Dehal, P;Satou, Y;Rokhsar, DS
通讯作者：
Rokhsar, DS