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Recurrent Evolutionary Innovations in Rodent and Primate Schlafen Genes.

Joris Mordier1, Marine Fraisse1, Michel Cohen-Tannoudji2

  • 1Institute of Genetics, Reproduction & Development (iGReD), CNRS UMR6293, INSERM U.1103, Université Clermont Auvergne, Clermont-Ferrand 63000, France.

Genome Biology and Evolution
|September 19, 2025
PubMed
Summary

Mammalian Schlafen genes, crucial for immunity and development, show varied evolution. Rapid evolution in protein domains interacting with viruses and other Schlafen proteins suggests adaptation to pathogens and gene family dynamics.

Keywords:
Schlafenduplicationgenetic conflictspositive selectionsubfunctionalization

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Area of Science:

  • Evolutionary biology
  • Genomics
  • Immunology

Background:

  • Schlafen proteins are vital RNase-related enzymes involved in immune and developmental processes.
  • Mammalian Schlafen genes exhibit diverse evolutionary conservation, impacting their functions.
  • Understanding the evolutionary innovations of Schlafen genes is crucial.

Purpose of the Study:

  • To characterize the evolutionary trajectories of mammalian Schlafen genes.
  • To identify the selective forces shaping Schlafen gene evolution.
  • To explore the functional implications of Schlafen gene evolution.

Main Methods:

  • Phylogenomic analyses to trace Schlafen gene evolution.
  • Analyses of lineage-specific gene amplifications and duplications.
  • Codon-level natural selection analyses in primates and rodents.
  • Integration of known and predicted protein structures.

Main Results:

  • Recent Schlafen duplicates evolved under distinct selective pressures, indicating subfunctionalization.
  • Positive selection was identified in Schlafen protein domains involved in viral interactions.
  • A novel class of rapidly evolving residues at Schlafen dimer interfaces suggests selection on protein compatibility.
  • Inter-Schlafen compatibility appears to be under strong selective pressure.

Conclusions:

  • Evolutionary innovations in mammalian Schlafen genes are likely driven by genetic conflicts with pathogens.
  • Interactions between Schlafen paralogs also contribute to their recurrent evolution.
  • Schlafen protein evolution impacts their molecular functions in immunity and development.