Portions of three male and two female candidate reproductive proteins believed to play a role in sperm and egg extracellular matrix interactions will be sequenced from a diverse range of placental mammals. This extensive database will be used in conjunction with molecular analyses to identify amino acid sites that are evolving rapidly and hence may be important in protein interactions. This rapid evolution will also be used to detect proteins or sites that may be coevolving. In addition, the database will be used to search for regions of conservation that may be important in protein structure and function. Characterizing these proteins and identifying their interactions will have a broader impact on diagnosing causes of infertility, understanding protein interactions conferring species-specificity and expanding the knowledge of protein co-evolution, which can be utilized in many other fields such as cancer research. This proposal presents a novel approach that takes advantage of the power of comparative genomics to characterize the proteins involved in mammalian fertilization. This project will afford opportunities for undergraduate volunteer participation in this exciting new bioinformatics field.