Mutations in cis-regulatory regions are important for adaptation and phenotypic evolution and have a low probability to generate negative pleiotropic effects (Swinnen et al., 2016; Meyer and Purugganan, 2013; Wray, 2007). FLM may be an ideal candidate for flowering time adaptation through non-coding sequence variation at PRO2+ and INT6+ sites since changes in FLM-ß abundance precisely modulate flowering while maintaining phenotypic plasticity and without generating negative pleiotropic effects (Figure 9). Changes at the PRO2+ and INT6+ sites should allow adapting flowering time in response to altered geographic distribution and consequently climate conditions as well as during changing global environments (Figure 9). The role of FLM orthologues in other Brassicaceae, including a number of agronomically important species, is as yet not understood. It is thus at present not possible to predict the role of Arabidopsis FLM polymorphisms for flowering time adaptation and plant breeding in this plant family. However, in view of the availability of new genome editing methodologies, the knowledge about important non-coding regions may be useful to fine-tune flowering time (Shan et al., 2013). This may allow buffering the anticipated negative effects on agricultural systems that occur as a consequence of small temperature changes during climate change (Moore and Lobell, 2015; Wheeler and von Braun, 2013).