Abstract
Bone morphogenetic proteins (BMPs) and the growth factors (GDFs) play an important role in ovarian folliculogenesis and essential regulator of processes of numerous granulosa cells. BMP15 gene variations linked to various ovarian phenotypic consequences subject to the species, from infertility to improved prolificacy in sheep, primary ovarian insufficiency in women or associated with minor subfertility in mouse. To study the evolving role of BMP15 and GDF9, a phylogenetic analysis was performed. To find out the candidate gene associated with prolificacy in mammals, the nucleotide sequence of BMP15 and GDF9 genes was recognized under positive selection in various mammalian species. Maximum‐likelihood approaches used on BMP15 and GDF9 genes exhibited a robust divergence and a prompted evolution as compared to other TGFβ family members. Furthermore, among 32 mammalian species, we identified positive selection signals in the hominidae clade resulting to 132D, 147E, 163Y, 191W, and 236P codon sites of BMP15 and 162F, 188K, 206R, 240A, 244L, 246H, 248S, 251D, 253L, 254F and other codon sites of GDF9. The positively selected amino acid sites such as Alanine, Lucien, Arginine, and lysine are important for signaling. In conclusion, this study evidences that GDF9 and BMP15 genes have rapid evolution than other TGFß family members and was subjected to positive selection in the mammalian clade. Selected sites under the positive selection are of remarkable significance for the particular functioning of the protein and consequently for female fertility.
Highlights
Ovarian folliculogenesis is essential for mammalian female fecundity and is regulated by a composite endocrine network between the pituitary and the ovary
As BMP15 and GDF9 play an important role in fertility and prolificacy, it means that consideration should be made to the gene sequences, that are generally accountable for the detected phenotypic variations
A huge number of conserved amino acids would mask the positive selection signals, and we found positive selection on variable amino acids which were exposed or buried residues according to the neural network algorithm BMP15 and GDF9
Summary
Ovarian folliculogenesis is essential for mammalian female fecundity and is regulated by a composite endocrine network between the pituitary and the ovary In this milieu, the intra-ovarian paracrine communications are important in oocyte development and follicle evolution and maturation and provide the tolerable sensitivity to gonadotrophic inducement. The bone morphogenetic protein 15 and growth differentiation factor 9, belong to the TGF-β superfamily, act on the granulosa cells to regulate oocyte growth and differentiation. These are expressed in all phases of follicle development in the mammalian species and are involved in steroidogenic regulation of granulosa cells (Dias, Khan, Adams, Sirard, & Singh, 2014; Peng et al, 2013). The objective of this study was to explore the selection signatures using maximum-likelihood approaches on the bases of molecular genetic difference of BMP15 and GDF9 among mammalian species with a view to provide applicable genetic information for marker assisted selection in the different species
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