Evolution of non-coding regulatory sequences involved in the developmental process: Reflection of differential employment of paralogous genes as highlighted by Sox2 and group B1 Sox genes

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概要

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• In higher vertebrates, the expression of <I>Sox2</I>, a group B1 <I>Sox</I> gene, is the hallmark of neural primordial cell state during the developmental processes from embryo to adult. <I>Sox2</I> is regulated by the combined action of many enhancers with distinct spatio-temporal specificities. DNA sequences for these enhancers are conserved in a wide range of vertebrate species, corresponding to a majority of highly conserved non-coding sequences surrounding the <I>Sox2</I> gene, corroborating the notion that the conservation of non-coding sequences mirrors their functional importance. Among the <I>Sox2</I> enhancers, N-1 and N-2 are activated the earliest in embryogenesis and regulate <I>Sox2</I> in posterior and anterior neural plates, respectively. These enhancers differ in their evolutionary history: the sequence and activity of enhancer N-2 is conserved in all vertebrate species, while enhancer N-1 is fully conserved only in amniotes. In teleost embryos, <I>Sox19a/b</I> play the major pan-neural role among the group B1 <I>Sox</I> paralogues, while strong <I>Sox2</I> expression is limited to the anterior neural plate, reflecting the absence of posterior CNS-dedicated enhancers, including N-1. In <I>Xenopus</I>, neurally expressed <I>SoxD</I> is the orthologue of <I>Sox19</I>, but <I>Sox3</I> appears to dominate other B1 paralogues. In amniotes, however, <I>Sox19</I> has lost its group B1 <I>Sox</I> function and transforms into group G <I>Sox15</I> (neofunctionalization), and <I>Sox2</I> assumes the dominant position by gaining enhancer N-1 and other enhancers for posterior CNS. Thus, the gain and loss of specific enhancer elements during the evolutionary process reflects the change in functional assignment of particular paralogous genes, while overall regulatory functions attributed to the gene family are maintained.<BR><BR>(Communicated by Takao SEKIYA, M.J.A.)

• 日本学士院の論文

著者

• Kondoh Hisato

  Graduate School Of Frontier Biosciences Osaka Univ.

• Uchikawa Masanori

  Graduate School Of Frontier Biosciences Osaka University

• Takemoto Tatsuya

  Graduate School Of Frontier Biosciences Osaka University

• KAMACHI Yusuke

  Graduate School of Frontier Biosciences, Osaka University

• IWAFUCHI Makiko

  Graduate School of Frontier Biosciences, Osaka University

• OKUDA Yuichi

  Graduate School of Frontier Biosciences, Osaka University

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