Evolutionary origin of Bone Morphogenetic Protein 15 and growth and differentiation factor 9 and differential selective pressure between mono- and polyovulating species

Olivier Monestier (1, 2) , Bertrand Servin (1, 2) , Sylvain Auclair (3) , Thomas Bourquard (3) , Anne Poupon (3) , Géraldine Pascal (1, 2) , Stéphane Fabre (1, 2)

1 GenPhySE - Génétique Physiologie et Systèmes d'Elevage
2 UT3 - Université Toulouse III - Paul Sabatier
3 PRC - Physiologie de la reproduction et des comportements [Nouzilly]

Bone morphogenetic protein 15 (BMP15) and growth and differentiation factor 9 (GDF9) are TGFbeta-like oocyte-derived growth factors involved in ovarian folliculogenesis as critical regulators of many granulosa cell processes and ovulation rate. Ovarian phenotypic effect caused by alterations in BMP15 and GDF9 genes appears to differ between species and may be relevant to their mono- or poly-ovulating status. Through phylogenetic analysis we recently showed that these two paralogous genes are strongly divergent and in rapid evolution as compared to other members of the TGFbeta superfamily. Here, we evaluate the amino-acid substitution rates of a set of proteins implicated in the ovarian function, including BMP15 and GDF9, with special attention to the mono- or poly-ovulating status of the species. Among a panel of mono- and poly-ovulating mammals, we demonstrate a better conservation of some areas in BMP15 and GDF9 within mono-ovulating species. Homology modeling of BMP15 and GDF9 homodimers and heterodimers 3D structures was suggestive that these areas may be involved in dimer formation and stability. A phylogenetic study of BMP15/GDF9 related proteins reveals that these two genes diverged from the same ancestral gene along with BMP3 and GDF10, two other paralogous genes. A substitution rate analysis based on this phylogenetic tree leads to the hypothesis of an acquisition of BMP15/GDF9 specific functions in ovarian folliculogenesis in mammals. We propose that high variations observed in specific areas of BMP15 and GDF9 in poly-ovulating species change the equilibrium between homodimers and heterodimers, modifying the biological activity and thus allowing poly-ovulation to occur.

Mots clés: molecular evolution; ovulation rate; phylogeny; selective pressure; substitution rate; bmp15; gdf9; tgfbeta; litter size

Domaines: Autre [q-bio.OT]

Olivier Monestier, Bertrand Servin, Sylvain Auclair, Thomas Bourquard, Anne Poupon, et al.. Evolutionary origin of Bone Morphogenetic Protein 15 and growth and differentiation factor 9 and differential selective pressure between mono- and polyovulating species. Biology of Reproduction, 2014, 91 (4), pp.1-13. ⟨10.1095/biolreprod.114.119735⟩. ⟨hal-01129871⟩