Coevolution within and between Regulatory Loci Can Preserve Promoter Function Despite Evolutionary Rate Acceleration

Phenotypes that appear to be conserved could be maintained not only by strong purifying selection on the underlying genetic systems, but also by stabilizing selection acting via compensatory mutations with balanced effects. Such coevolution has been invoked to explain experimental results, but has rarely been the focus of study. Conserved expression driven by the unc-47 promoters of Caenorhabditis elegans and C. briggsae persists despite divergence within a cis-regulatory element and between this element and the trans-regulatory environment. Compensatory changes in cis and trans are revealed when these promoters are used to drive expression in the other species. Functional changes in the C. briggsae promoter, which has experienced accelerated sequence evolution, did not lead to alteration of gene expression in its endogenous environment. Coevolution among promoter elements suggests that complex epistatic interactions within cis-regulatory elements may facilitate their divergence. Our results offer a detailed picture of regulatory evolution in which subtle, lineage-specific, and compensatory modifications of interacting cis and trans regulators together maintain conserved gene expression patterns.

看似保守的表型，不仅可通过对底层遗传系统发挥作用的强纯化选择（purifying selection）得以维持，也可通过经由具有平衡效应的补偿突变（compensatory mutations）发挥作用的稳定选择（stabilizing selection）得以维持。这类协同进化（coevolution）曾被用于解释实验结果，但却极少成为研究的核心对象。秀丽隐杆线虫（Caenorhabditis elegans）与布氏隐杆线虫（Caenorhabditis briggsae）的unc-47启动子所驱动的表达模式虽保守，但顺式调控元件（cis-regulatory element）内部以及该元件与反式调控环境（trans-regulatory environment）之间已发生分化。当将这两种启动子互换以驱动另一物种的基因表达时，便可观察到顺式与反式层面的补偿性变化。经历了序列加速进化的布氏隐杆线虫启动子，其功能变化并未在其内源环境中引发基因表达的改变。启动子元件间的协同进化表明，顺式调控元件内部复杂的上位性互作（epistatic interactions）或可推动其发生分化。本研究结果为调控进化提供了一幅细致图景：相互作用的顺式与反式调控因子通过细微的、谱系特异性的以及补偿性的修饰，共同维持了保守的基因表达模式。