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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 non-immune physiology through engagement with immune system genes. This raises a logical question of how genetically promiscuous is the immune system; here defined as how heavily cross-referenced is the immune system into other physiological systems? Here, we examine immune gene promiscuity across physiological systems in primates by examining the baseline (unperturbed) expression of key tissue and cell types for expression differences, and primate genomes for signatures of selection. We found “immune” gene expression to be cross-referenced extensively in other physiological systems in primates. When immune and non-immune tissues diverge in expression, the differentially expressed genes at baseline are enriched for cell biological activities not immediately identifiable as immune function-based. Individual comparisons of immune and non-immune 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. We also see positive selection in the coding regions of differentially 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.

Supplementary_TableS1.xlsx (13 kB)
Supplementary Table S1. Sequence Data (FASTQ) Used in the Analysis

Supplementary_TableS2.xlsx (48 kB)
Supplementary Table S2. Consistently Expressed Immune Genes (counts per million normalized value of <ME>10 ) in Primate Nonimmune Tissues

Supplementary_TableS3.xlsx (18457 kB)
Supplementary Table S3. Differentially Expressed Genes

Supplementary_TableS4.xlsx (243 kB)
Supplementary Table S4. Results from Enrichment Analysis of Significantly Differentially Expressed (DE) Genes Generated by Immune versus Nonimmune Tissue Contrast

Supplementary_TableS5.xlsx (6970 kB)
Supplementary Table S5. Results from Enrichment Analysis of Significantly Differentially Expressed (DE) Genes Generated by Pairwise Tissue Contrasts

Supplementary_TableS6.xlsx (983 kB)
Supplementary Table S6. dN/dS Values and Enrichments for Primates, Hominoids, and Humans