Diversity of Bmp15 and Gdf9 Genes in White Goat of Guizhou Province and Evolution of the Encoded Proteins

Members of the transforming growth factor-beta superfamily, growth differentiation factor 9 (GDF9) and bone morphogenetic protein 15 (BMP15), have crucial roles in fecundity of sheep. Our previous investigation confirmed that the fecundity mutations of sheep presented in highly prolific White goat individuals of Guizhou province. To illuminate other polymorphisms in Bmp15 and Gdf9 genes and the relationship of these mutations with function, we set out to clone and characterize the coding region of Bmp15 and Gdf9. Molecular models of BMP15 and GDF9 mature peptide of White goat were constructed based on the homology to experimental tertiary structure of human BMP7. Two exons encoded prepropeptide of 394 amino acids in BMP15 and 453 residues in GDF9, respectively. Apart from the FecX^B mutation (S99I) in BMP15 and V79I mutation in GDF9 confirmed in White goat previously, other seven and three polymorphism sites were detected from BMP15 and GDF9 mature peptides, respectively. S32G, N66H, S99I/P99I and G107R in BMP15 could be important for the binding of dimer to receptors. Changes of P78Q and V79I in GDF9 might affect the binding of dimer to receptor type 1. Comparing the length of BMP15 and GDF9 prepropeptide in vertebrates, an increase in length of BMP15 presented along with the protein evolution from fish to mammal and the divergence of the N-terminus residues in matured BMP15 peptide might contribute to the sensitive control on the fertility of animal species with low ovulation rate. These findings gave a valuable explanation for the correlation of mutations in Bmp15 and Gdf9 genes with the control on fecundity of White goat and supported the notion that they were the pivotal factors in female fertility of White goat in Guizhou province.