Tracking the Rules of Transmission and Introgression with Networks

It has been proposed that an organism and its microbes form an assemblage called a holobiont ( 1 , 2 ). The human body and human genome along with gut microbes and their genomes can be seen as a dynamic holobiont system ( 3 – 5 ), i.e., a superorganism amalgamating microbial and human attributes ( 6 ). In this multipartite holobiont, the host genome provides the primary genome, while microbial genes constitute the “second human genome,” which is in fact a prokaryotic pangenome ( 3 , 7 , 8 ). Whether the holobionts are units of selection is actively debated ( 9 – 11 ), yet other aspects of their biology are less controversial, and holobionts are becoming a major object of study in biology. Among these uncontroversial features lies the observation that, by definition, a holobiont is home to several different modes of genetic transmission. In nuclear transmission, the genetic material is inherited from one individual (in parthenogenesis, for example) or, most of the time, from two individuals, whereas in organelle transmission (of mitochondria, for example), the material is mostly inherited from the mother, in animals ( 12 ). Both types of transmission result directly from the reproduction of the host. This stands in contrast to transmission of the microbiota, that is, the acquisition (or loss) of microbes between host generations. In mammals, at birth, the microbiota is inherited from the mother, but this is not always the case for other animal groups, where it could also be inherited from the environment ( 12 , 13 ). During the life of the individual, the microbiota may even evolve, depending on different factors, which are currently not well characterized (e.g., host constraints, diet, environment, and transmission between different hosts) ( 14 ). The transmission of microbiomes differs in turn from the transmission of microbiotas, since it is no longer (or at least not only) microbes that are exchanged, acquired, or lost, but genes themselves. These genes may be carried by microbes, but also by viruses, plasmids, or other classes of mobile genetic elements (MGEs). For example, transmissions in the gut microbiome are in part due to horizontal gene transfer (HGT) ( 4 , 15 , 16 ) because of the high cell density in microorganisms, and mediated by viruses—especially temperate prophages ( 17 , 18 )—integrases, recombinases ( 19 ), and conjugative transposons ( 20 ). Finally, the transmission of microbes from the environment to the host has not been systematically taken into account ( 11 ). As with any transmission, microbial transmission can be transient or permanent ( Fig. 1 ).