Protein Evolution

Functional Relevance of Proteins for Male Fertility

For thousends of murine and human proteins we calculated a score giving their individual Fertility Relevance Probability (FRP). The FRP score is intended as a criterion based on which reproductive biologists and physicians can select genes or proteins as diagnostic and therapeutic targets in cases of male sub- and infertility.

The results are presented in a paper (Greither et al. 2020) and at

The score can take any value between 0 and 1: the higher it is, the more likely a protein should be important for the maintenance of male fertility. For its inference, we used clinical data as well as parameters giving the functional relevance of a protein, such as its connectivity in a protein-protein interaction network, transcript abundance and evolutionary conservation.

The Impact of Mating Systems

We study the evolution of sperm-egg interaction in the light of sexual selection taking mating systems and physical measures as proxies of species-specific levels of male competition. Much of our work focused on the evolution of sperm ligands called zonadhesin (ZAN) and sperm adhesion molecule 1 (SPAM1) that both interact with female molecules. These analyses revealed that species-specific evolutionary rates (dN/dS) of the genes encoding ZAN and SPAM1 are lower in primate species with stronger sexual dimorphism of body weight (Herlyn and Zischler 2007; Prothmann et al. 2012).

Towards the Full Picture

In another study, we showed that increased functional constraint due to more interaction partners in the protein-protein network is the probable reason for stronger conservation of phosphorylated sperm proteins (Schumacher et al. 2013). Follow-up investigations confirmed that differences in mating systems and connectivity in the protein-protein interaction network correlate with evolutionary rates of genes encoding sperm and testis proteins (e.g., Schumacher et al. 2014). In sperm proteins, we further observed that increased transcript abundance and phyletic age correlate with higher evolutionary conservation (Schumacher and Herlyn 2018). Also, involvements in basic cellular processes associate with higher evolutionary conservation (Schumacher et al. 2017). Last but not least, we found that the closer their function is to fertilization, the less proteins engage in the formation of internal structures (Kwiatkowski et al 2020). Unraveling these relationships is important for more precise predictions of the relevance of proteins and their coding genes for male fertility.

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