Analysis of cis-regulatory evolution for the paralogous genes and failsafe networks

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We have studied regulatory mechanisms of vertebrate Pax2, Pax5 and Pax5 genes, which have evolved from a single ancestral gene of early cephalochordates. It is known that the three Pax genes exhibit distinct but overlapping expression during the ear, brain and kidney development, and interact each other in the co-expressed tissues. We compared human, chicken and Xenopus genomic sequences and identified 55 conserved noncoding sequences(CNSs) for Pax2, 19 for Pax5 and 6 for Pax8. We subjected the CNSs to the high-throughput co-transgenesis assay in Xenopus, identified 13 active kidney enhancers for Pax2. We also identified the one of the Pax2 kidney enhancers is activated in response to reduction of paralogous genes.