Intrinsically disordered BMP4 morphogen and the beak of the finch: Co-option of an ancient axial patterning system.

Darwin's finches, with the primary diversity in the shape and size of their beaks, represent an excellent model system to study speciation and adaptive evolution. It is generally held that evolution depends on the natural selection of heritable phenotypic variations originating from the genetic mutations. However, it is now increasingly evident that epigenetic transgenerational inheritance of phenotypic variation can also guide evolutionary change. Several studies have shown that the bone morphogenetic protein BMP4 is a major driver of beak morphology. A recent study explored variability of the morphological, genetic, and epigenetic differences in the adjacent "urban" and "rural" populations of two species of Darwin's finches on the Galápagos Islands and revealed significant changes in methylation patterns in several genes including those involved in the BMP/TGFß pathway in the sperm DNA compared to erythrocyte DNA. These observations indicated that epigenetic changes caused by environmental fluctuations can be passed on to the offspring. Nonetheless, the mechanism by which dysregulated expression of BMP4 impacts beak morphology remains poorly understood. Here, we show that BMP4 is an intrinsically disordered protein and present a causal a link between epigenetic changes, BMP4 dysregulation and the evolution of the beak of the finch by natural selection.