Gene regulatory network architecture in different developmental contexts influences the genetic basis of morphological evolution

Convergent phenotypic evolution is often caused by recurrent changes at particular nodes in the underlying gene regulatory networks (GRNs). The genes at such evolutionary ‘hotspots’ are thought to maximally affect the phenotype with minimal pleiotropic consequences. This has led to the suggestion that if a GRN is understood in sufficient detail, the path of evolution may be predictable. The repeated evolutionary loss of larval trichomes among Drosophila species is caused by the loss of shavenbaby (svb) expression. svb is also required for development of leg trichomes, but the evolutionary gain of trichomes in the ‘naked valley’ on T2 femurs in Drosophila melanogaster is caused by reduced microRNA-92a (miR-92a) expression rather than changes in svb. We compared the expression and function of components between the larval and leg trichome GRNs to investigate why the genetic basis of trichome pattern evolution differs in these developmental contexts. We found key differences between the two networks in both the genes employed, and in the regulation and function of common genes. These differences in the GRNs reveal why mutations in svb are unlikely to contribute to leg trichome evolution and how instead miR-92a represents the key evolutionary switch in this context. Our work shows that variability in GRNs across different developmental contexts, as well as whether a morphological feature is lost versus gained, influence the nodes at which a GRN evolves to cause morphological change. Therefore, our findings have important implications for understanding the pathways and predictability of evolution.

趋同表型进化通常由底层基因调控网络（gene regulatory networks, GRNs）中特定节点的反复变异所驱动。这类进化‘热点’位点上的基因被认为能够以最小的多效性代价最大化地影响表型。基于此，有学者提出假说：若能充分解析某一基因调控网络的细节，进化路径或可被预测。果蝇属物种中幼虫表皮毛的重复进化丢失，均由shavenbaby（svb）基因的表达缺失所导致。svb同时也是腿部表皮毛发育所必需的基因，但黑腹果蝇（Drosophila melanogaster）中胸股骨‘裸区’表皮毛的进化新增，并非由svb的序列或表达改变引起，而是源于微小RNA-92a（microRNA-92a, miR-92a）的表达下调。我们对比了幼虫与腿部表皮毛基因调控网络各组分的表达模式与功能，旨在探究为何表皮毛模式进化的遗传基础在这两种发育情境中存在差异。研究发现，这两套调控网络在所使用的核心基因、共有基因的调控机制与功能层面均存在关键差异。这些基因调控网络的差异揭示了两个核心问题：其一，为何svb突变不太可能参与腿部表皮毛的进化；其二，miR-92a为何可作为该情境下的关键进化开关。本研究表明，不同发育情境下基因调控网络的固有差异性，以及形态特征是发生丢失还是新增，共同决定了基因调控网络发生进化以引发形态改变的节点位置。因此，本研究结果对于理解进化路径及其可预测性具有重要的理论意义。