Evolved tooth gain in sticklebacks is associated with a cis-regulatory allele of Bmp6
Evolved tooth gain in sticklebacks is associated with a cis-regulatory allele of Bmp6
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DOI：
10.1073/pnas.1407567111
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发表时间：
2014-09-23
影响因子：
11.1
通讯作者：
Miller, Craig T.
中科院分区：
文献类型：
--
作者：
Cleves, Phillip A.;Ellis, Nicholas A.;Miller, Craig T.
形态学进化差异的发育遗传学研究导致了顺式调控变化往往是形态学进化的基础的假设。然而，由于这些研究大多集中在性状的进化丧失上，因此对遗传结构及其与增益性状顺式调控变化的可能关联的了解较少。在这里，我们展示了一个衍生的底栖淡水棘鱼种群已经进化出了大约两倍的腹咽牙齿数量与他们的祖先海洋同行相比。对比实验室饲养的低齿海洋种群和高齿底栖种群的发育过程，发现在幼年后期出现齿数和齿板面积的增加和齿间距的减小。全基因组连锁图谱确定了影响牙齿模式不同方面的大量独立的数量性状位点。一个控制牙齿数量的大效定量性状位点精确定位到一个包含优秀候选基因骨形态发生蛋白6 （Bone morphogenetic protein 6, Bmp6）的基因组区域。刺鱼Bmp6在发育中的牙齿中表达，并且在高齿和低齿种群之间没有发现编码变化。然而，在F1杂交体发育牙齿中Bmp6等位基因的定量特异性表达分析表明，顺式调控变化在棘鱼发育后期而非早期提高了淡水底栖生物Bmp6等位基因的相对表达水平。总的来说，我们的数据支持一个模型，即Bmp6表达的晚作用顺式调控上调是衍生底栖刺鱼牙齿数量显著增加的基础。
Developmental genetic studies of evolved differences in morphology have led to the hypothesis that cis-regulatory changes often underlie morphological evolution. However, because most of these studies focus on evolved loss of traits, the genetic architecture and possible association with cis-regulatory changes of gain traits are less understood. Here we show that a derived benthic freshwater stickleback population has evolved an approximate twofold gain in ventral pharyngeal tooth number compared with their ancestral marine counterparts. Comparing laboratory-reared developmental time courses of a low-toothed marine population and this high-toothed benthic population reveals that increases in tooth number and tooth plate area and decreases in tooth spacing arise at late juvenile stages. Genome-wide linkage mapping identifies largely separate sets of quantitative trait loci affecting different aspects of dental patterning. One large-effect quantitative trait locus controlling tooth number fine-maps to a genomic region containing an excellent candidate gene, Bone morphogenetic protein 6 (Bmp6). Stickleback Bmp6 is expressed in developing teeth, and no coding changes are found between the high-and low-toothed populations. However, quantitative allele-specific expression assays of Bmp6 in developing teeth in F1 hybrids show that cis-regulatory changes have elevated the relative expression level of the freshwater benthic Bmp6 allele at late, but not early, stages of stickleback development. Collectively, our data support a model where a late-acting cis-regulatory up-regulation of Bmp6 expression underlies a significant increase in tooth number in derived benthic sticklebacks.