The interaction between a microbiome and its host species, and the impact of this interaction on both bacterium and host organism evolution, is a fascinating subject. Known as the hologenome theory of evolution, it has been widely understood that microbiome communities and their animal hosts undergo natural selection in concert. In other words, human and microbiome evolutionary processes are not mutually exclusive. In the hope of gaining a deeper understanding of this relationship, a recent study published in Nature Communications examined the exact role of the microbiome in host speciation of a vertebrate organism. Researchers explored evolutionary divergence within two subspecies of mice and examined to what extent genetic loci played a role in regulating intestinal microbiota populations.
Four strains of mice were used to develop a unique mouse model paradigm. Researchers collected two naturally occurring and genetically distinct mouse populations – M.m. musculus and M.m. domesticus –that are geographically isolated in Europe (see map). Interestingly, a small “hybrid zone” exists in which both subspecies interbreed. Researchers examined these three distinct populations and added a fourth by artificially producing a hybrid strain between both subspecies under strict laboratory conditions. The purpose of the laboratory-bred hybrid was to control for any confounding influence from environmental factors (it has been demonstrated that environment can influence microbiome populations and gene expression). A subsequent analysis was performed to investigate intestinal microbiome genetic profiles for both pure species and hybrid species in addition to gene expression with potential connection to pathological indications in host species.
Pyrosequencing techniques of a bacterial rRNA gene were used to identify genetic differences between pure species and “naturally occurring” wild-hybrid species. Bacteria community structure varied significantly in hybrid generations, both those obtained from the hybrid zone and bred in the lab. The most significant differences were observed in the laboratory-bred hybrid generation. Furthermore, there was a significant decrease in bacterium species richness in both wild and lab hybrid mice. QTL mapping, a technique used to assess underlying genetic factors, displayed a low number of microbiota genomic loci present in both hybrid strains. This finding was thought to explain a 14.1% variation in bacterial community structure, ultimately suggesting that genetic deficiencies disrupted microbiome communities.
QTL profiling of microbiota also indicated a high frequency of genes implicated in immune system regulation. Laboratory hybrid generations were shown to have imbalanced T-cell subset populations at various immune sites (e.g. spleen, mesenteric lymph nodes) in combination with the aforementioned alterations in bacterium community structure. Additionally, histological analysis of intestinal mucosa revealed significant increases in inflammatory cell infiltrates and epithelial ulcerations in both wild and lab hybrid mice as compared to both purebred wild species. The investigators suggest a discrepancy in communication between microbiome populations and the host immune cells.
The data from this study suggest abnormal genetic architecture and irregular immune function result in an altered intestinal microbiome due to cross-breeding between two vertebrate subspecies. The hybrid species displayed poor fitness for survival. As suggested by the authors, species divergence, and the consequentially genetic disruptions resulting in an altered microbiota population, is perhaps responsible for generating subspecies population isolation. This theory offers a possible explanation or contributing factor as to why M.m. musculus and M.m. domesticus populations are geographically distinct. Obviously, evolutionary biology is an enormously complex process with many diverse and distinct influences. However, as this article proposes, perhaps the microbiome has had a much more profound influence on evolutionary fate than we previously realized.