Genetic Variation in the Immune System of Old World Monkeys: Functional and Selective Effects

Abstract

Pathogen-mediated selection has played an important role in human and nonhuman primate evolution. Differences in infectious disease susceptibility within species, as well as species-specific differences, are in part due to differences in the immune response to pathogens. Elucidating the genetic basis of these differences is therefore an integral component of understanding the evolutionary origin and maintenance of primate phenotypic variation. Old World monkeys (OWMs) are excellent candidates for this line of research. Many OWM species are abundant in the wild, and as a result of long-term field studies of these populations, demographic, life history, and behavioral characteristics that may influence disease susceptibility are well characterized. Additionally, several OWM species are common in captivity and have become major medical models for human disease. Here, we outline the motivations for work on immune system genetic variation in OWMs and review existing knowledge about the selective import and functional effects of this variation. First, we focus on evidence for natural selection within the OWM immune system, including recent genome-scale scans for positive selection. We also discuss current gaps in our understanding of OWM immune system evolution, with particular attention to natural selection outside of coding regions and intraspecific selection. Natural selection on genetic variation implies that this variation also has fitness-related phenotypic consequences. Thus, we next discuss the use of functional assays to investigate the mechanisms that relate genetic variation to phenotype. We present examples of studies in OWMs that have successfully integrated functional and evolutionary genetic analyses in order to understand immune system diversity, spanning research focused on differences between major OWM taxonomic groups, between species, and between individuals within contemporary OWM populations. We conclude by briefly assessing future directions for the field.