BACKGROUND Cell differentiation is mediated by synchronized waves of coordinated expression for hundreds to thousands of genes, and must be regulated to produce complex tissues and phenotypes. For many animal species, sexual selection has driven the development of elaborate male ornaments, requiring sex-specific differentiation pathways. One such male ornament is the pheromone-producing mental gland of the red-legged salamander (Plethodon shermani). Mental gland development follows an annual cycle of extreme hypertrophy, production of pheromones for the ~ 2 month mating season, and then complete resorption before repeating the process in the following year. At the peak of the mating season, the transcriptional and translational machinery of the mental gland are almost exclusively redirected to the synthesis of rapidly evolving pheromones. Of these pheromones, Plethodontid Modulating Factor (PMF) has experienced an unusual history: following gene duplication, the protein coding sequence diversified from positive sexual selection while the untranslated regions have been conserved by purifying selection. The molecular underpinnings that bridge the processes of gland hypertrophy, pheromone synthesis, and conservation of the untranslated regions remain to be determined. RESULTS Using Illumina sequencing, we prepared a de novo transcriptome of the mental gland at six stages of development. Differential expression analysis and immunohistochemistry revealed that the mental gland initially adopts a highly proliferative, almost tumor-like phenotype, followed by a rapid increase in pheromone mRNA and protein. One likely player in this transition is Cold Inducible RNA Binding Protein (CIRBP), which selectively and cooperatively binds the highly conserved PMF 3' UTR. CIRBP, along with other proteins associated with stress response, have seemingly been co-opted to aid in mental gland development by helping to regulate pheromone synthesis. CONCLUSIONS The P. shermani mental gland utilizes a complex system of transcriptional and post-transcriptional gene regulation to facilitate its hypertrophication and pheromone synthesis. The data support the evolutionary interplay of coding and noncoding segments in rapid gene evolution, and necessitate the study of co-evolution between pheromone gene products and their transcriptional/translational regulators. Additionally, the mental gland could be a powerful emerging model of regulated tissue proliferation and subsequent resorption within the dermis and share molecular links to skin cancer biology.

中文翻译：

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红脚sal精神腺的基因调节的年度周期：从肥大到快速进化的信息素的表达。

背景技术细胞分化是由数百至数千个基因的协调表达的同步波介导的，并且必须被调节以产生复杂的组织和表型。对于许多动物而言，性别选择驱动了精致的雄性装饰品的发展，需要特定于性别的分化途径。一种这样的雄性装饰品是红脚sal（Plethodon shermani）产生信息素的精神腺。精神腺的发育遵循一个极端的肥大的年度循环，在约两个月的交配季节产生信息素，然后完全吸收，然后在第二年重复该过程。在交配季节的高峰期，精神腺的转录和翻译机制几乎完全重定向到快速进化的信息素的合成上。在这些信息素中，Plethodontid调节因子（PMF）经历了一段不寻常的历史：基因复制后，蛋白质编码序列从有性选择中多样化，而未翻译的区域通过纯化选择得以保存。桥接腺体肥大，信息素合成和未翻译区域保守性的分子基础尚待确定。结果使用Illumina测序，我们在发育的六个阶段制备了脑腺的从头转录组。差异表达分析和免疫组织化学显示，精神腺最初采用高度增殖的，几乎是肿瘤样的表型，然后信息素mRNA和蛋白迅速增加。在此过渡过程中，一个可能的参与者是冷诱导RNA结合蛋白（CIRBP），选择性地和协同地结合高度保守的PMF 3'UTR。CIRBP以及与应激反应相关的其他蛋白质似乎已被选为通过帮助调节信息素的合成来帮助精神腺发育。结论沙门氏疟原虫利用复杂的转录和转录后基因调控系统，以促进其营养过度和信息素合成。数据支持编码和非编码片段在快速基因进化中的进化相互作用，并且有必要研究信息素基因产物与其转录/翻译调节子之间的共同进化。另外，