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首页> 外文期刊>PLoS Genetics >Early Evolution of Conserved Regulatory Sequences Associated with Development in Vertebrates
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Early Evolution of Conserved Regulatory Sequences Associated with Development in Vertebrates

机译:与脊椎动物发育相关的保守调控序列的早期进化

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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.
机译:各种脊椎动物基因组之间的比较发现了成千上万个高度保守的非编码序列,其中越来越多的非编码序列已显示在早期发育中起增强子的作用。尽管它们在人类和软骨鱼类之间经过5亿年的极端保护,但这些元素在无脊椎动物中似乎基本上不存在,并且迄今为止,人们对它们的作用方式或模仿它们的进化过程了解甚少。现在,我们已经利用了海七Petro鳗(Petromyzon marinus)的新兴基因组序列数据,来探索最早存在的现存脊椎动物谱系无颚鱼(无颌鱼类)中这类元素的保护深度。我们在13个人类基因位点搜索保守的非编码元件(CNEs),并确定了与除了这些基因区域中的两个以外的所有其他区域相关的七lamp鳗元件。尽管与颚状脊椎动物相比,其显着更短且保存性更差,但已鉴定的七lamp鳗CNE能够驱动斑马鱼胚胎中的特定表达模式,这与由等效人类元素驱动的表达模式几乎相同。因此,这些CNE是所有脊椎动物的独特特征。此外,七lamp鳗与其他脊椎动物CNE的比对应允许鉴定负责常见表达模式并有助于阐明CNE中调节语言的持久序列特征。确定所有脊椎动物共有的核心发育调控代码,为构建调控网络奠定了基础,并可能阐明在基因组DNA中有多大的保守调控序列块进化并固定下来。

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