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

我们研究了脊椎动物Pax2， Pax5和Pax5基因的调控机制，这些基因是从早期头脊索动物的单一祖先基因进化而来的。已知这三种Pax基因在耳朵、大脑和肾脏发育过程中表现出不同但重叠的表达，并在共表达组织中相互作用。我们比较了人类、鸡和爪蟾的基因组序列，鉴定出55个Pax2、19个Pax5和6个Pax8的保守非编码序列。我们将CNSs置于爪蟾的高通量共转基因实验中，鉴定出13种Pax2活性肾增强子。我们还发现其中一个Pax2肾增强子被激活以响应旁系基因的减少。

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.