We live in a world dominated by viruses; those causing disease in humans are painfully familiar to us, but little is known about most viruses harbored within a person, what scientists refer to as ‘viral dark matter’. The majority of these human-associated viruses are actually phages that infect bacteria in the gut. To determine the origins of the phage communities in the human gut, we set out to describe the phages of our closest living relatives, non-human primates. This comparative study published in PNAS examined the gut phages in 23 wild primate species living in very different ecosystems across the globe, as well as from humans living in Europe and Africa.

Surprisingly, we found relatives of most human associated phages in wild primates! When we then looked at the evolutionary relationships of these phage lineages, they found that for many, the relationships of phages were a near mirror image of the evolutionary history of the primates. This pattern of co-divergence suggests that some phages maintained an association with specific primate lineages over millions of years. We sometimes observe patterns of co-divergence between primates and the viruses that infect them, demonstrating that some viruses maintain a close relationship with their hosts over evolutionary timescales. But phages infect bacteria, not primate cells, and we were rather surprised to find that some phages also showed such a pattern.

We then set out to determine how such long-term associations between primates and their phages are maintained. We found that neighboring social groups of baboons harbored unique phage communities, with close grooming partners having more similar phage communities, even after controlling for similarities in the baboon’s bacterial communities and the genetic relationship of the baboons. This study really highlights the importance of long-term observational studies of wild primates, like the Amboseli Baboon Research Project, to answer questions that are actually quite difficult to address in humans. These baboon groups have been followed for decades and we know their genealogy and their grooming partners, with scientists frequently collecting fecal samples. Such a resolution of data simply does not exist for human populations. These findings certainly suggest that human social relationships might also influence phage transmission, but proving this will require more research.

The team set out to understand how flexible the association of primates and their phages are by studying the phages of primates in zoos, as well as the phages of their zookeepers. Captive primates lost the phages they normally harbor in the wild, with those phages all replaced by human-associated ones. Considering that wild primates seem to have maintained their phages over millions of years of evolutionary history, we were really surprised to find that great apes that have only lived in captivity for a generation or two, have completely lost these phage lineages via replaced by human-associated ones.

This study provides insights into the evolutionary and ecological origins of our associated ‘viral dark matter’ and opens up exciting avenues of research. It suggests phages can serve as a marker of microbial transmission at the human wildlife interface, providing a much-needed tool to identify high-risk areas for pathogen transmission. The part of this study focusing on captive great apes highlights that between species transmission of phages is feasible – now we need to understand whether and where it occurs in the wild and what impact these phages have on primate and human health.

This study was an international collaborative effort with scientists in Germany working at the Robert Koch Institute, Christian-Albrecht-University of Kiel, the Max Planck Institute for Evolutionary Biology, and the Max Planck Institute for Evolutionary Anthropology, as well as colleagues from the University of Neuchatel in Switzerland, the Université Alassane Ouattara de Bouake in the Côte d’Ivoire, the National Institute for Biomedical Research in the Democratic Republic of the Congo, and the University of Notre Dame, Duke University, and Harvard University in the USA, and many organizations working with long-term primates in the field. Thanks to all these wonderful collaborators.

Original publication: Gogarten, J. F., Rühlemann, M., Archie, E., Tung, J., Akoua-Koffi, C., Bang, C., Deschner, T., Muyembe-Tamfun, J.-J., Robbins, M. M., Schubert, G., Surbeck, M., Wittig, R. M., Zuberbühler, K., Baines, J. F., Franke, A., Leendertz, F. H., and Calvignac-Spencer, S., Primate phageomes are structured by superhost phylogeny and environment. Proceedings of the National Academy of Sciences of the United States of America. doi: 10.1073/pnas.2013535118/