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Evolution of CEACAM1 N Domain Biologically Active Sites in Primates.

Keith M Skubitz1,2, Wolfgang Zimmermann3

  • 1Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN 55455, USA.

Biology
|December 30, 2025
PubMed
Summary

Researchers compared CEACAM1 N domain sequences across primates, finding variations in active peptides. These differences, particularly in bonobos and humans, may impact neutrophil activity and pathogen interactions.

Keywords:
CD66aCD66bCD66cCD66dCEACEACAM1CEACAM3CEACAM6CEACAM8evolutionneutrophilpeptide

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Area of Science:

  • Immunology
  • Evolutionary Biology
  • Genetics

Background:

  • Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) regulate immune responses and act as pathogen entry points.
  • CEACAM1's N domain contains peptides with human neutrophil stimulatory activity.
  • Understanding CEACAM1 evolution is crucial for its diverse physiological roles.

Purpose of the Study:

  • To compare CEACAM N domain and active peptide sequences among primates.
  • To identify sequence variations potentially affecting human neutrophil activity.
  • To explore evolutionary pressures shaping CEACAM1 function.

Main Methods:

  • Comparative sequence analysis of CEACAM N domains across selected primate species.
  • Amino acid sequence comparison of five biologically active CEACAM1 N domain peptides.
  • Identification of single nucleotide polymorphisms (SNPs) and resulting amino acid changes in human populations.

Main Results:

  • High similarity of CEACAM1 N domains within primate groups (apes, Old World monkeys, New World monkeys, lemurs/tarsiers).
  • Observed amino acid differences in active peptides among species, some predicted to reduce human neutrophil activity.
  • Specific amino acid changes in CD66a-1, CD66a-2, and CD66a-3 regions found in bonobos and/or human populations, with some unique to humans.

Conclusions:

  • Primate CEACAM1 N domains show conserved structure but exhibit species-specific variations in active peptide sequences.
  • Observed variations, particularly in bonobos and humans, may alter neutrophil activation and susceptibility to pathogens.
  • Unidentified pathogen selective pressure could drive these evolutionary differences in CEACAM1, potentially leading to population-specific effects.