Adikusuma Fatwa, Pederick Daniel, McAninch Dale, Hughes James, Thomas Paul
School of Biological Sciences, University of Adelaide, South Australia, Australia 5005.
The Robinson Research Institute, University of Adelaide, South Australia, Australia 5005.
Genetics. 2017 Jul;206(3):1495-1503. doi: 10.1534/genetics.117.202549. Epub 2017 May 17.
Gene duplication provides spare genetic material that evolution can craft into new functions. and are evolutionarily related genes with overlapping and unique sites of expression during embryogenesis. It is currently unclear whether SOX2 and SOX3 have identical or different functions. Here, we use CRISPR/Cas9-assisted mutagenesis to perform a gene-swap, replacing the ORF with the ORF to investigate their functional equivalence in the brain and testes. We show that increased expression of SOX2 can functionally replace SOX3 in the development of the infundibular recess/ventral diencephalon, and largely rescues pituitary gland defects that occur in null mice. We also show that ectopic expression of SOX2 in the testes functionally rescues the spermatogenic defect of null mice, and restores gene expression to near normal levels. Together, these data provide strong evidence that SOX2 and SOX3 proteins are functionally equivalent.
基因复制提供了备用的遗传物质，进化过程可以将其塑造为新的功能。[基因名称1]和[基因名称2]是在胚胎发生过程中具有重叠和独特表达位点的进化相关基因。目前尚不清楚SOX2和SOX3是否具有相同或不同的功能。在这里，我们使用CRISPR/Cas9辅助诱变进行基因交换，用[基因名称2]的开放阅读框（ORF）替换[基因名称1]的ORF，以研究它们在大脑和睾丸中的功能等效性。我们发现，SOX2表达的增加在漏斗隐窝/腹侧间脑的发育中可以在功能上替代SOX3，并在很大程度上挽救了[基因名称1]基因敲除小鼠中出现的垂体缺陷。我们还表明，SOX2在睾丸中的异位表达在功能上挽救了[基因名称1]基因敲除小鼠的生精缺陷，并将基因表达恢复到接近正常水平。总之，这些数据提供了有力证据，证明SOX2和SOX3蛋白在功能上是等效的。
