Human evolution, spit by spit
Saliva is needed for the pre-processing of food in the mouth, the maintenance of tooth mineralization, and protection from microbial pathogens. What is known to date about the functions of salivary proteins has largely been deduced from conventional in vitro experiments or by analogy to distantly related animal models that only incompletely represent the human condition with respect to saliva. This gap in knowledge also poses an impediment to harnessing saliva as a diagnostic fluid for dental and systemic diseases. An alternative approach to gaining insights into the functions and disease associations of salivary proteins is to conduct comparative studies of globally distinct human populations or with closely related primate species. When we compared the proteomes of human saliva and the saliva of our closest extant evolutionary relatives, chimpanzees and gorillas, we found that humans produce a waterier saliva, containing less than half the total protein of great apes and Old-World monkeys. We also discovered unique protein profiles in human saliva that were distinct from those of nonhuman primates. By analyzing the evolution of genes encoding key saliva proteins across the mammalian lineage, we found that saliva-related genes have undergone frequent duplications, losses, and regulatory changes, with these patterns becoming particularly evident in the primate lineage. These findings open up the possibility that dietary differences and pathogenic pressures may have shaped a uniquely distinct salivary proteome in the human lineage. Overall, our work highlights the evolutionary malleability of saliva-related genes and provides new insights into how adaptations to diet and disease may have influenced primate biology. Discovering such variations will allow future studies to elucidate adaptations to human-specific dietary changes and to new pathogen challenges that emerged with increased meat consumption beginning over 2 million years ago, and more recently with agriculture, animal husbandry, and sedentarism.
