Shaping of developmental gradients through selection on multiple loci in Antirrhinum

Development depends on precise shaping of molecular gradients, but how natural selection acts to establish precision is unknown. Here, we analyze genes that control differences in the gradient of yellow flower color between two varieties of snapdragon (Antirrhinum). We show that these differences depend, in part, on cis-regulatory variation in the pigment biosynthetic gene, FLAVIA (FLA). FLA interacts multiplicatively with three other loci, one of which is a trans-acting regulator of FLA, to further shape the yellow gradient. All the loci exhibit clines at a hybrid zone, with widths that correlate with phenotypic effect, showing how selection can hone gradient shape with remarkable precision by acting on cis and trans variation at multiple loci.