Early origin of the human seminal plasma proteome during vertebrate evolution

Seminal Fluid Proteins (SFPs)-encoding genes are rapidly evolving at the sequence level and often considered prone to frequent phylogenetic turnover. One mechanism underlying such rapid turnover is the lineage-restricted origin of new SFP genes, which results in a complement of phylogenetically young genes. Recent advances in genome resources and comparative genomics now enable more comprehensive cross-taxa analyses, providing improved estimates of the timing of gene origin during evolution. Using these resources alongside proteomic data from human seminal plasma, we traced the evolutionary origins of 646 putative human SFP genes. We find that most SFPs trace back to the bony vertebrate (Eutelostomi) radiation. These ancient SFP genes are more pleiotropic than younger ones, which are enriched in immunity-related functions and regulate proteolytic activity, particularly peptidase inhibitors. Together, these results underscore that the human proteome components of the seminal plasma were originated early during vertebrate evolution, providing insights into the history of the reproductive biology in deuterostomes.