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颈动物的单个祖先基因进化而来的。众所周知，这三个Pax基因在耳、脑和肾发育过程中表现出不同但重叠的表达，并在共同表达的组织中相互作用。我们比较了人、鸡和爪哇的基因组序列，确定了Pax2、Pax5和Pax8的55个保守非编码序列(CNS)，19个和6个。我们对CNSS进行了高通量共转基因实验，鉴定了13个Pax2的活性肾脏增强剂。我们还鉴定了其中一个Pax2肾脏增强子被激活，以响应平行基因的减少。

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.