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The Origin and Evolution of Sex Peptide and Sex Peptide Receptor Interactions

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Peng, Junhui, Svetec, Nicolas, Molina, Henrik, Zhao, Li·2024·Molecular Biology and Evolution
DOI 10.1093/molbev/msae065PMC PMC11017328

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Abstract

Post-mating responses play a vital role in successful reproduction across diverse species. In fruit flies, sex peptide binds to the sex peptide receptor, triggering a series of post-mating responses. However, the origin of sex peptide receptor predates the emergence of sex peptide. The evolutionary origins of the interactions between sex peptide and sex peptide receptor and the mechanisms by which they interact remain enigmatic. In this study, we used ancestral sequence reconstruction, AlphaFold2 predictions, and molecular dynamics simulations to study sex peptide–sex peptide receptor interactions and their origination. Using AlphaFold2 and long-time molecular dynamics simulations, we predicted the structure and dynamics of sex peptide–sex peptide receptor interactions. We show that sex peptide potentially binds to the ancestral states of Diptera sex peptide receptor. Notably, we found that only a few amino acid changes in sex peptide receptor are sufficient for the formation of sex peptide–sex peptide receptor interactions. Ancestral sequence reconstruction and molecular dynamics simulations further reveal that sex peptide receptor interacts with sex peptide through residues that are mostly involved in the interaction interface of an ancestral ligand, myoinhibitory peptides. We propose a potential mechanism whereby sex peptide–sex peptide receptor interactions arise from the preexisting myoinhibitory peptides–sex peptide receptor interface as well as early chance events both inside and outside the preexisting interface that created novel sex peptide-specific sex peptide–sex peptide receptor interactions. Our findings provide new insights into the origin and evolution of sex peptide–sex peptide receptor interactions and their relationship with myoinhibitory peptides–sex peptide receptor interactions.

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Metadata

Authors
Peng, J., Svetec, N., Molina, H., & Zhao, L.
Affiliations
Rockefeller University (US)
Corresponding author
Zhao, Li
ORCID
Venue
Molecular Biology and Evolution
Publisher
Oxford University Press (OUP)
Published
2024-03-22
Volume
41
Issue
4
ISSN
  • 0737-4038 (ISSN-L)
  • 1537-1719
DOI
10.1093/molbev/msae065
PMC
PMC11017328
OpenAlex
W4393064703
Cited by
9
References
9
Citations by year
2026: 4 · 2025: 3 · 2024: 2
FWCI
1.57
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Biology and Evolution (publishedVersion, cc-by-nc)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc)
Funders
  • National Institutes of Health (R35GM133780)
  • Robertson Foundation
  • Paul G. Allen Family Foundation
  • Rita Allen Foundation
  • Vallee Scholar Program
  • C. H. Li Memorial Scholar
  • Rockefeller University
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
Keywords
sex peptide, sex peptide receptor, post-mating response, myoinhibitory peptides, protein-protein interaction, ancestral sequence reconstruction, Diptera, fruit flies, protein structure prediction, molecular dynamics simulation

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