Background: Organisms evolve complex traits by recruiting existing programs to new contexts, referred as co-option. Within a species, single upstream regulators can trigger full differentiation programs. Distinguishing whether co-option of differentiation programs results from variation in single regulator, or in multiple genes, is key for understanding how complex traits evolve. As an experimentally accessible model for studying this question we turned to budding yeast, where a differentiation program (filamentous) is activated in S. cerevisiae only upon starvation, but used by the related species S. paradoxus also in rich conditions. Results: To define expression variations associated with species-specific activation of the filamentous program, we profiled the transcriptome of S. cerevisiae, S. paradoxus and their hybrid along two cell cycles at 5-minutes resolution. As expected in cases of co-option, expression of oscillating genes varies between the species in synchrony with their growth phenotypes and was dominated by upstream trans-variations. Focusing on regulators of filamentous growth, we identified gene-linked variations (cis) in multiple genes across regulatory layers, which propagated to affect expression of target genes, as well as binding specificities of downstream transcription factor. Unexpectedly, variations in regulators essential for S. cerevisiae filamentation were individually too weak to explain activation of this program in S. paradoxus. Conclusions: Our study reveals the complex architecture of regulatory variation associated with species-specific use of a differentiation program. Based on these results, we suggest a new model in which evolutionary co-option of complex traits is stabilized in a distributed manner through multiple weak-effect variations accumulating throughout the regulatory network.

中文翻译：

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绘制监管变化的架构图可洞悉复杂特征的演变

背景：生物体通过招募现有的程序到新的环境中来发展复杂的特征，这被称为“共同选择”。在一个物种内，单个上游调节剂可以触发完整的分化程序。区分分化程序的共同选择是由单个调节子还是多个基因的变异决定的，这是理解复杂性状如何进化的关键。作为研究此问题的实验上可行的模型，我们转向了发芽酵母，其中酿酒酵母中的分化程序（有丝）仅在饥饿时被激活，而相关物种悖论链霉菌也可在丰富条件下使用。结果：为了定义与物种特异性激活丝状程序相关的表达变异，我们分析了酿酒酵母S.的转录组。悖论及其杂种沿着两个细胞周期以5分钟的分辨率传播。正如在共同选择的情况下所预期的那样，不同物种之间的振荡基因表达与其生长表型同步变化，并由上游的反式变异主导。着眼于丝状生长的调控因子，我们在调控层中鉴定了多个基因的基因连锁变异（cis），这些变异传播影响目标基因的表达以及下游转录因子的结合特异性。出乎意料的是，酿酒酵母丝化所必需的调节剂的变化太弱，无法解释该程序在悖论链球菌中的激活。结论：我们的研究揭示了与物种特异性使用分化程序有关的调控变异的复杂结构。根据这些结果，