Immune system promiscuity in human and nonhuman primate evolution

Jessica F. Brinkworth, Courtney C. Babbitt

Research output: Contribution to journalArticlepeer-review


Many genes that respond to infection have functions outside of immunity and have been found to be under natural selection. Pathogens may therefore incidentally alter nonimmune physiology through engagement with immune system genes. This raises a logical question of how genetically promiscuous the immune system is, here defijined as how heavily cross-referenced the immune system is into other physiological systems. This work examined immune gene promiscuity across physiological systems in primates by assessing the baseline (unperturbed) expression of key tissue and cell types for diffferences, and primate genomes for signatures of selection. These effforts revealed “immune” gene expression to be cross-referenced extensively in other physiological systems in primates. When immune and nonimmune tissues diverge in expression, the diffferentially expressed genes at baseline are enriched for cell biological activities not immediately identifijiable as immune function based. Individual comparisons of immune and nonimmune tissues in primates revealed low divergence in gene expression between tissues, with the exception of whole blood. Immune gene promiscuity increases over evolutionary time, with hominoids exhibiting the most cross-referencing of such genes among primates. An assessment of genetic sequences also found positive selection in the coding regions of diffferentially expressed genes between tissues functionally associated with immunity. This suggests that, with increasing promiscuity, divergent gene expression between the immune system and other physiological systems tends to be adaptive and enriched for immune functions in hominoids.

Original languageEnglish (US)
Pages (from-to)251-269
Number of pages19
JournalHuman biology
Issue number4
StatePublished - Sep 1 2018


  • Evolutionary immunology
  • Immune promiscuity
  • Immune system
  • Pleiotropy
  • Primate immunity
  • Primate immunogenomics

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Genetics(clinical)


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