Dominant Gut Bacteria Accelerate Gene Evolution in the Human Microbiome

Evolutionary tweaks to the genome tend to occur slowly, emerging over thousands of years. Yet a sudden environmental change can also spark a rapid genetic mutation. Microbes are especially prone to this genetic plasticity, evolving strategies to trigger and enhance such mutations.

Mobile genetic elements called diversity-generating retroelements (DGRs) can make quick work of mutating a short region of a gene, given some rapid environmental catalyst. As a result, DGRs can pack an abundance of variation into targeted genes and ultimately change a protein’s function. 

Researchers have known that these promiscuous elements dynamically move around DNA, hopping in and out of the genome. But little is known about DGR biology and its potential significance in the human gut microbiome. 

Now, new evidence suggests that DGRs play a dominant role in the accelerated evolution of certain genes in the gastrointestinal environment. In a paper published this week in Science, researchers report that this evolution occurs in real-time as microbes are transferred from mother to infant during childbirth. Such results could inform future research on the link between the maternal microbiota and infant health. 

MBL Assistant Scientist Blair Paul, an expert on DGRs, and John Mekalanos of Harvard Medical School, co-authored a Science Perspective on the new research, which was conducted primarily at the University of California, Los Angeles.  

An abundance of variance  

Using genomic tools from human datasets and experimental mouse models, researchers characterized a major group of DGRs in the gastrointestinal environment in the genus Bacteroides. They found that DGRs were particularly dominant in this bacterial genus, hypermuting specific “target” genes in the human microbiota. 

These Bacteroides microbes are incredibly diverse, with “quite a stunning number of DGRs per genome,” said Paul. 

The results, Paul said, suggest that these dominant DGRs are hyperactive and affect proteins that are important to human gut bacteria and viruses. 

Moreover, metagenomic analyses from human datasets revealed that large numbers of DGRs are transferred from mother to infant during childbirth. Specifically, a group of Bacteroides DGRs are more prevalent in infants delivered vaginally, compared to infants delivered through cesarean section. 

Perhaps, Paul speculated, these DGRs from Bacteroides are more active, hypermutating during delivery. From there, it may be that specific gene variants that arose from DGR mutation are favored over other sequences. 

“When it comes to microbial diversity, there are certain ones that end up being selected for and thriving. Maybe it’s DGRs that are helping them get to that point to be selected for and thrive,” said Paul. Further research is needed to determine the specific health implications of these DGR-driven mutations.

So much of this research is complicated by the interconnected, dynamic web of microbial interactions flourishing in the microbiota. Still, it’s an “exciting step,” Paul said. And more evidence of the many elegant ways nature has found to affect maximum evolutionary change in an environment.