A recurrent regulatory change underlying altered expression and Wnt response of the stickleback armor plates gene EDA.
A recurrent regulatory change underlying altered expression and Wnt response of the stickleback armor plates gene EDA.
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DOI：
10.7554/elife.05290
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发表时间：
2015-01-28
期刊：
影响因子：
7.7
通讯作者：
Kingsley DM
中科院分区：
文献类型：
--
作者：
O'Brown NM;Summers BR;Jones FC;Brady SD;Kingsley DM
Armor plate changes in sticklebacks are a classic example of repeated adaptive evolution. Previous studies identified ectodysplasin (EDA) gene as the major locus controlling recurrent plate loss in freshwater fish, though the causative DNA alterations were not known. Here we show that freshwater EDA alleles have cis-acting regulatory changes that reduce expression in developing plates and spines. An identical T → G base pair change is found in EDA enhancers of divergent low-plated fish. Recreation of the T → G change in a marine enhancer strongly reduces expression in posterior armor plates. Bead implantation and cell culture experiments show that Wnt signaling strongly activates the marine EDA enhancer, and the freshwater T → G change reduces Wnt responsiveness. Thus parallel evolution of low-plated sticklebacks has occurred through a shared DNA regulatory change, which reduces the sensitivity of an EDA enhancer to Wnt signaling, and alters expression in developing armor plates while preserving expression in other tissues. DOI: http://dx.doi.org/10.7554/eLife.05290.001 Stickleback fish develop bony plates on their surface to protect themselves from predators. The extent and pattern of their bony armor depends on their habitat: marine sticklebacks are typically covered from head to tail with bony plates, but freshwater sticklebacks retain only a few plates on their sides. One gene that promotes the formation of the bony plates is called ectodysplasin (EDA). This encodes a signaling protein that is important for the development of the skeleton, skin and many other tissues. Variations in the sequence of this gene are shared among different stickleback populations worldwide. However, it has not been clear which genetic changes can explain how lightly armored freshwater sticklebacks could have evolved from their well-armored marine ancestors on several separate occasions. Here, O'Brown et al. studied EDA in marine and groups of freshwater sticklebacks that have evolved in different locations around the world. The experiments show that the level of expression of EDA in the developing plates and spines is lower in the freshwater fish. O'Brown et al. thought this could be due to genetic changes in regions of EDA that lie outside the region that encodes the protein, so called ‘regulatory elements’. Indeed, further experiments found that all freshwater fish have a small change in the DNA of a regulatory element that switches on the gene in plate-forming regions of the body. When this change was introduced into marine sticklebacks, the fish had lower levels of gene expression in these plate-forming regions. These findings demonstrate that lightly armored sticklebacks have evolved multiple times from their well-armored marine ancestors through the same small change in their DNA that alters the expression of the EDA gene. The next challenge will be to understand why this particular small change in DNA appears to be favored over all the other changes that could occur in the regulatory element, and to see if factors that act through this regulatory switch also modify armor structures in natural populations. DOI: http://dx.doi.org/10.7554/eLife.05290.002
