Howard Hughes Medical Institute and Laboratory of Molecular Biology, University of Wisconsin, Madison, WI 53706, USA.
Proc Natl Acad Sci U S A. 2011 Jun 21;108(25):10036-43. doi: 10.1073/pnas.1105937108. Epub 2011 May 18.
Spatiotemporal changes in gene expression underlie many evolutionary novelties in nature. However, the evolutionary origins of novel expression patterns, and the transcriptional control elements ("enhancers") that govern them, remain unclear. Here, we sought to explore the molecular genetic mechanisms by which new enhancers arise. We undertook a survey of closely related Drosophila species to identify recently evolved novel gene expression patterns and traced their evolutionary history. Analyses of gene expression in a variety of developing tissues of the Drosophila melanogaster species subgroup revealed high rates of expression pattern divergence, including numerous evolutionary losses, heterochronic shifts, and expansions or contractions of expression domains. However, gains of novel expression patterns were much less frequent. One gain was observed for the Neprilysin-1 (Nep1) gene, which has evolved a unique expression pattern in optic lobe neuroblasts of Drosophila santomea. Dissection of the Nep1 cis-regulatory region localized a newly derived optic lobe enhancer activity to a region of an intron that has accumulated a small number of mutations. The Nep1 optic lobe enhancer overlaps with other enhancer activities, from which the novel activity was co-opted. We suggest that the novel optic lobe enhancer evolved by exploiting the cryptic activity of extant regulatory sequences, and this may reflect a general mechanism whereby new enhancers evolve.
时空变化中的基因表达是自然界中许多进化新特征的基础。然而，新的表达模式的进化起源，以及控制它们的转录调控元件（“增强子”），仍然不清楚。在这里，我们试图探索新增强子出现的分子遗传机制。我们对密切相关的果蝇物种进行了调查，以鉴定最近进化的新基因表达模式，并追踪它们的进化历史。对黑腹果蝇物种亚组各种发育组织中的基因表达分析表明，表达模式的分化率很高，包括许多进化上的丧失、异时性转变，以及表达域的扩张或收缩。然而，新的表达模式的获得要少得多。一个例子是 Neprilysin-1 (Nep1) 基因，它在果蝇 santomea 的视神经原细胞中进化出了独特的表达模式。对 Nep1 顺式调控区的剖析将一个新衍生的视神经增强子活性定位到一个内含子区域，该区域积累了少量突变。Nep1 视神经增强子与其他增强子活性重叠，新的活性是从这些活性中共同获得的。我们认为，新的视神经增强子是通过利用现存调控序列的隐匿活性进化而来的，这可能反映了新增强子进化的一般机制。
