123 Genomic insights into the evolution of cytokine tissue specificity across primates

Faculty Mentor: Timothy Webster (Anthropology)

Cytokines are immune glycoproteins released in a hormone-like manner to promote the regulation of the inflammatory response upon pathogen recognition. As such, their dysregulation has been linked to several physiological disorders, including autoimmune diseases. While their medical importance has been well-established, far less is known about their evolutionary patterns. In this study, we used RNA-seq data from heart, kidney, liver, and lung tissue samples collected from the same individuals of three primate species: human (Homo sapiens), chimpanzee (Pan troglodytes), and rhesus macaque (Macaca mulatta). We measured the expression of 314 previously annotated cytokine genes and quantified tissue specificity of expression using the tau metric. We found that rhesus macaques (τmean=0.840; τmedian=0.886) demonstrated, overall, a greater degree of tissue specificity than humans (τmean=0.807; τmedian=0.861) and chimpanzees (τmean=0.790; τmedian=0.813) (Urhesus-human=64287.5, p=0.0297; Urhesus-chimp=55322, p=0.00042), while humans and chimpanzees did not differ significantly (Uhuman-chimp=112288, p=0.122). Our ongoing analyses build on these results by investigating the degree to which tissue-specific cytokines maintain their specificity across lineages, provide insight into the evolutionary patterns of individual cytokine genes. Together, these results will contribute to our understanding of the evolution of primate immune responses.