Characterizing patterns of selection pressure on mammalian antiviral immune response

Abstract

Immune response is known to be under constant evolutionary pressure from different factors including pathogens. Although different selection regimes are expected to act on the magnitude of immune response, there are limited studies that have investigated the different patterns of selection pressures on the immune response quantitatively. I employed evolutionary models (Ornstein-Uhlenbeck models) to identify different patterns of selection on the antiviral immune response of fibroblasts derived from 18 mammalian species and one vertebrate stimulated by viral ligand, poly I: C, or Interferon alpha cytokine. I found stabilizing selection to be the dominant form of selection on the immune response. Out of 59 genes that were found to be responding in at least 15 species, 50 genes were found to be under stabilizing selection. Moreover, the evolutionary variance was found to differ among these conservatively responding genes implicated in fighting viruses. For instance, ADAR was found to have low evolutionary variance while TRIM14 response showed the opposite trend suggesting different evolutionary pressures acting on the magnitude of response. Directional selection was also detected in specific infra-orders of primates such as apes and old-world monkeys in response of innate immune effectors.