Sex peptide (SP), a seminal fluid protein of  Drosophila melanogaster males, has been described as driving a virgin-to-mated switch in females, through eliciting an array of responses including increased egg laying, activity, and food intake and a decreased remating rate. While it is known that SP achieves this, at least in part, by altering neuronal signaling in females, the genetic architecture and temporal dynamics of the female’s response to SP remain elusive. We used a high-resolution time series RNA-sequencing dataset of female heads at 10 time points within the first 24 h after mating to learn about the genetic architecture, at the gene and exon levels, of the female’s response to SP. We find that SP is not essential to trigger early aspects of a virgin-to-mated transcriptional switch, which includes changes in a metabolic gene regulatory network. However, SP is needed to maintain and diversify metabolic changes and to trigger changes in a neuronal gene regulatory network. We further find that SP alters rhythmic gene expression in females and suggests that SP’s disruption of the female’s circadian rhythm might be key to its widespread effects.

Sex Peptide, a seminal fluid protein of D. melanogaster males, has been described as driving a virgin-to-mated switch in females, through eliciting an array of responses, including increased egg laying, activity and food intake and a decreased re-mating rate. While it is known that Sex Peptide achieves this, at least in part, by altering neuronal signaling in females, the identity of key molecular regulators that act downstream of Sex Peptide is not known. Here, we used a high-resolution time series RNA-sequencing dataset of female heads at 10 time points within the first 24 hours after mating to investigate the genetic architecture, at the gene- and exon-level, of the female’s response to Sex Peptide. We find that Sex Peptide is not essential to trigger a virgin-to-mated transcriptional switch, which involves changes in a metabolic gene regulatory network. However, Sex Peptide is needed to maintain and diversify metabolic changes and to trigger changes in a neuronal gene regulatory network. We further find that Sex Peptide might interact with the female’s circadian clock to orchestrate transcriptional changes across different regulatory networks. That a male seminal fluid protein can alter a female’s rhythmic gene expression has implications for our understanding of both reproductive and circadian behaviors.