We found a uniform distribution of nine PRO2+/INT6+ haplotype combinations among the genetic clusters that have recently been established based on the analysis of genomic sequences from 1135 Arabidopsis accessions (The 1001 Genomes Consortium, 2016). Interestingly, the PRO2+GGAAC/INT6+AAT haplotype was overrepresented among the relict accessions and the PRO2+AAAAC/INT6+AAA haplotype was overrepresented among the Asian group (The 1001 Genomes Consortium, 2016) (Figure 8—figure supplement 1). In our experiments, both of these haplotypes were associated with increased FLM-ß transcript levels and consequently late flowering (Figure 4). Since the relict and Asian accessions have been proposed to originate from glacial refugia from where central Europe was recolonized after the last ice age, these late-flowering PRO2+/INT6+ haplotypes may represent original haplotypes (Sharbel et al., 2000; Schmid et al., 2006). The late flowering phenotype associated with these haplotypes would be in line with the hypothesis that late flowering alleles are more ancient and that early flowering alleles were derived only during the more recent Arabidopsis evolution (Toomajian et al., 2006). Further, genetic linkage among the PRO2+ and INT6+ polymorphic sites was overall low (R2 = 0.11–0.55) and the sequences surrounding PRO2+ and INT6+ were comparatively conserved. Taken together, this suggests that mutations in the PRO2+ and INT6+ sites independently arose multiple times and that these sites were preferentially selected during Arabidopsis flowering adaptation. All PRO2+/INT6+ alleles displayed a broad geographic distribution, except PRO2+GGAAC/INT6+AAT, which was overrepresented in Spain (Figure 8—figure supplement 1). Likely, microclimates at specific geographic locations rather than general climate conditions at broad geographic regions may be important to drive adaptation of flowering to changing ambient temperature, as it was previously suggested for broadly distributed non-coding haplotypes of FLC that explain variation in vernalization (Li et al., 2014; Weigel, 2012; Shindo et al., 2006).