贵州白山羊Bmp15和Gdf9基因多态性及其编码蛋白的进化分析(英文)

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

BMP15和GDF9是转化生长因子β(TGFβ)超家族的成员,对绵羊的繁殖性状有直接的调节作用,从中发现的多个高产突变位点直接提高了排卵数和产羔数。在之前的研究中,作者从贵州白山羊中找到了一个高产突变位点。为了进一步揭示Bmp15和Gdf9基因突变与繁殖性状之间的关系,对贵州白山羊Bmp15和Gdf9基因编码区进行了克隆,以人BMP7的晶体结构为模板构建了贵州白山羊BMP15和GDF9成熟肽的三维模型。贵州白山羊Bmp15和Gdf9基因分别编码394和453个氨基酸的蛋白前体。对BMP15和GDF9成熟肽序列进行分析发现,除了之前确认的BMP15中的FecXB突变(S99I)和GDF9中的V79I突变之外,还从贵州白山羊的BMP15和GDF9成熟肽分别发现7个和3个位点突变。其中,BMP15成熟肽的S32G、N66H、S99I/P99I和G107R突变可能影响二聚体与受体的结合;GDF9成熟肽的P78Q和V79I影响二聚体与I型受体的亲和力,将值得进一步深入研究。对Bmp15和Gdf9基因编码的蛋白前体序列进行聚类分析,结果显示在鱼类到哺乳类的进化过程中,BMP15出现长度逐渐增加的现象,以BMP15成熟肽N端长度增加为主。这种演变可能使BMP15对低排卵哺乳动物繁殖力的控制更为灵敏。该文的研究结果为贵州白山羊Bmp15和Gdf9基因变异与繁殖力的关系提出了合理的解释,并支持这两个因子是贵州白山羊高产性状重要调节因子的观点。

Members of the transforming growth factor-beta superfamily, growth differentiation factor 9 （GDF9） and bone morphogenetic protein 15 （BMP 15）, 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 Bmpl5 and Gdfl） genes and the relationship of these mutations with function, we cloned and characterized the coding region of Bmp15 and Gdfl）. Molecular models of BMP15 and GDF9 mature peptide of White goat were constructed based on the homology of human BMP7 experimental tertiary structure. Two exons encoded prepropeptide of 394 amino acids in BMPI5 and 453 residues in GDF9, respectively. Apart from the FecXs mutation （S99I） in BMP15 and V791 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 t. Comparing the length of BMP 15 and GDF9 prepropeptide in vertebrates, an increase in length of BMP 15 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 Bmpl5 and Gdfl） 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.