Laboratory mice (Mus musculus domesticus) harbor gut bacterial strains that are distinct from those of wild mice but whose evolutionary histories are unclear. Here, we show that laboratory mice have retained gut bacterial lineages that diversified in parallel (co-diversified) with rodent species for > 25 million years, but that laboratory-mouse gut microbiota (LGM) strains of these ancestral symbionts have experienced accelerated accumulation of genetic load during the past ~ 120 years of captivity. Compared to closely related wild-mouse gut microbiota (WGM) strains, co-diversified LGM strains displayed significantly faster genome-wide rates of nonsynonymous substitutions, indicating elevated genetic drift—a difference that was absent in non-co-diversified symbiont clades. Competition experiments in germ-free mice further indicated that LGM strains within co-diversified clades displayed significantly reduced fitness in vivo compared to WGM relatives to an extent not observed within non-co-diversified clades. Thus, stochastic processes (e.g., bottlenecks), not natural selection in the laboratory, have been the predominant evolutionary forces underlying divergence of co-diversified symbiont strains between laboratory and wild house mice. Our results show that gut bacterial lineages conserved in diverse rodent species have acquired novel mutational burdens in laboratory mice, providing an evolutionary rationale for restoring laboratory mice with wild gut bacterial strain diversity.
Publication Link: https://www.nature.com/articles/s41467-025-57435-z