In higher vertebrates, the expression of
Sox2, a group B1
Sox gene, is the hallmark of neural primordial cell state during the developmental processes from embryo to adult.
Sox2 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
Sox2 gene, corroborating the notion that the conservation of non-coding sequences mirrors their functional importance. Among the
Sox2 enhancers, N-1 and N-2 are activated the earliest in embryogenesis and regulate
Sox2 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,
Sox19a/b play the major pan-neural role among the group B1
Sox paralogues, while strong
Sox2 expression is limited to the anterior neural plate, reflecting the absence of posterior CNS-dedicated enhancers, including N-1. In
Xenopus, neurally expressed
SoxD is the orthologue of
Sox19, but
Sox3 appears to dominate other B1 paralogues. In amniotes, however,
Sox19 has lost its group B1
Sox function and transforms into group G
Sox15 (neofunctionalization), and
Sox2 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.
(Communicated by Takao SEKIYA, M.J.A.)
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