Evolved Bmp6 enhancer alleles drive spatial shifts in gene expression during tooth development in sticklebacks.
Evolved Bmp6 enhancer alleles drive spatial shifts in gene expression during tooth development in sticklebacks.
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DOI：
10.1093/genetics/iyab151
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发表时间：
2021-12-10
期刊：
影响因子：
3.3
通讯作者：
Miller CT
中科院分区：
文献类型：
--
作者：
Stepaniak MD;Square TA;Miller CT
增强子的突变已被证明通常是自然变异的基础，但增强子活性的进化差异可能很难在体内识别。三刺刺鱼（Gasterosteus aculeatus）由于丰富的自然遗传变异、祖先海洋和衍生的淡水形式之间的进化表型多样性以及转基因技术的易处理性而成为研究增强子进化的强大系统。先前的工作鉴定了骨形态发生蛋白6（Bmp6）基因的内含子增强子内的一系列多态性，这些多态性与进化的牙齿增加有关，牙齿增加是发育后期出现的淡水牙齿数量的衍生增加。在这里，我们使用包含遗传绝缘体和一对相互双色转基因报告系的双顺反子报告构建体来比较该增强子的海洋和淡水等位基因的增强子活性。在老年鱼中，这两个等位基因在发育中的牙齿的间质和上皮中驱动部分重叠的表达，但相对于海洋增强子，淡水增强子驱动减少的间充质结构域和更大的上皮结构域。在较年轻的鱼中，增强子活性的这些空间变化不太明显。通过原位杂交比较海洋和淡水鱼牙齿发育过程中 Bmp6 的表达，揭示了基因表达中相似的进化空间变化。总之，这些数据支持一个模型，其中该增强子内的多态性是通过在牙齿发育过程中改变 Bmp6 的空间表达来进化牙齿增益的基础，并提供了识别体内增强子活性的空间差异的一般策略。
Mutations in enhancers have been shown to often underlie natural variation but the evolved differences in enhancer activity can be difficult to identify in vivo. Threespine sticklebacks (Gasterosteus aculeatus) are a robust system for studying enhancer evolution due to abundant natural genetic variation, a diversity of evolved phenotypes between ancestral marine and derived freshwater forms, and the tractability of transgenic techniques. Previous work identified a series of polymorphisms within an intronic enhancer of the Bone morphogenetic protein 6 (Bmp6) gene that are associated with evolved tooth gain, a derived increase in freshwater tooth number that arises late in development. Here, we use a bicistronic reporter construct containing a genetic insulator and a pair of reciprocal two-color transgenic reporter lines to compare enhancer activity of marine and freshwater alleles of this enhancer. In older fish, the two alleles drive partially overlapping expression in both mesenchyme and epithelium of developing teeth, but the freshwater enhancer drives a reduced mesenchymal domain and a larger epithelial domain relative to the marine enhancer. In younger fish, these spatial shifts in enhancer activity are less pronounced. Comparing Bmp6 expression by in situ hybridization in developing teeth of marine and freshwater fish reveals similar evolved spatial shifts in gene expression. Together, these data support a model in which the polymorphisms within this enhancer underlie evolved tooth gain by shifting the spatial expression of Bmp6 during tooth development, and provide a general strategy to identify spatial differences in enhancer activity in vivo.
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影响因子：
3.3
作者：
Albert, Arianne Y. K.;Sawaya, Sterling;Schluter, Dolph
通讯作者：
Schluter, Dolph
DOI：
10.1098/rspb.2014.0822
发表时间：
2014-08-07
影响因子：
4.7
作者：
Erickson, Priscilla A.;Glazer, Andrew M.;Miller, Craig T.
通讯作者：
Miller, Craig T.
DOI：
10.1073/pnas.1407567111
发表时间：
2014-09-23
影响因子：
11.1
作者：
Cleves, Phillip A.;Ellis, Nicholas A.;Miller, Craig T.
通讯作者：
Miller, Craig T.
影响因子：
48
作者：
Cranfill PJ;Sell BR;Baird MA;Allen JR;Lavagnino Z;de Gruiter HM;Kremers GJ;Davidson MW;Ustione A;Piston DW
通讯作者：
Piston DW
影响因子：
64.5
作者：
CHUNG, JH;WHITELEY, M;FELSENFELD, G
通讯作者：
FELSENFELD, G