Figure 7.

A model for the role of Bmp6 cis-regulatory changes in underlying evolved tooth gain in sticklebacks. (A) Quantitative trait loci (QTL) and fine mapping previously revealed variants in intron 4 of Bmp6 that were associated with evolved tooth gain in freshwater fish (Cleves et al. 2014, 2018; Miller et al. 2014). These variants are adjacent to a previously characterized minimal enhancer (lavender) that was shown to drive expression in tooth epithelium and mesenchyme (Cleves et al. 2018). Six core single nucleotide polymorphisms (SNPs, depicted as red and blue lines within the modifier sequence) showed complete concordance with a large effect tooth number QTL (Cleves et al. 2018). (B) Marine and freshwater enhancers have different spatial activity, with the derived freshwater allele driving less mesenchymal expression, but more epithelial expression relative to the marine allele. (C) Consistent with the different enhancer activity, Bmp6 expression by in situ hybridization is reduced in the mesenchyme but expanded in the epithelium in freshwater teeth relative to marine teeth. (D) We hypothesize that the enhancer alleles (A) have spatially shifted enhancer activity (B), resulting in shifts in Bmp6 expression overall (C), and evolved tooth gain in freshwater fish (D).