Tracking the Rules of Transmission and Introgression with Networks.

Understanding how an animal organism and its gut microbes form an integrated biological organization, known as a holobiont, is becoming a central issue in biological studies. Such an organization inevitably involves a complex web of transmission processes that occur on different scales in time and space, across microbes and hosts. Network-based models are introduced in this chapter to tackle aspects of this complexity and to better take into account vertical and horizontal dimensions of transmission. Two types of network-based models are presented, sequence similarity networks and bipartite graphs. One interest of these networks is that they can consider a rich diversity of important players in microbial evolution that are usually excluded from evolutionary studies, like plasmids and viruses. These methods bring forward the notion of "gene externalization," which is defined as the presence of redundant copies of prokaryotic genes on mobile genetic elements (MGEs), and therefore emphasizes a related although distinct process from lateral gene transfer between microbial cells. This chapter introduces guidelines to the construction of these networks, reviews their analysis, and illustrates their possible biological interpretations and uses. The application to human gut microbiomes shows that sequences present in a higher diversity of MGEs have both biased functions and a broader microbial and human host range. These results suggest that an "externalized gut metagenome" is partly common to humans and benefits the gut microbial community. We conclude that testing relationships between microbial genes, microbes, and their animal hosts, using network-based methods, could help to unravel additional mechanisms of transmission in holobionts.