New method to study Crohn’s disease microbes
The reverse ecology method is likely to be applied in the near future to studying the full diversity of the bacteria that inhabit the human body.
Identifying species among plants and animals has been a full-time occupation for some biologists, but the task is even more daunting for the myriad microbes that inhabit the planet. Now, MIT researchers have developed a simple measurement of gene flow that can define ecologically important populations among bacteria and archaea, including pinpointing populations associated with human diseases.
The gene flow metric separates co-existing microbes in genetically and ecologically distinct populations, Martin Polz, a professor of civil and environmental engineering at MIT, and colleagues write in the August 8 issue of Cell.
Polz and his colleagues also developed a method to identify parts of the genome in these populations that show different adaptations that can be mapped onto different environments. When they tested their approach on a gut bacterium, for instance, they were able to determine that different populations of the bacteria were associated with healthy individuals and patients with Crohn’s disease.
Biologists often call a group of plants or animals a species if the group is reproductively isolated from others — that is, individuals in the group can reproduce with each other, but they can’t reproduce with others. As a result, members of a species share a set of genes that differs from other species. Much of evolutionary theory centers on species and populations, the representatives of a species in a particular area.
But microbes “defy the classic species concept for plants and animals,” Polz explains. Microbes tend to reproduce asexually, simply splitting themselves in two rather than combining their genes with other individuals to produce offspring. Microbes are also notorious for “taking up DNA from environmental sources, such as viruses,” he says. “Viruses can transfer DNA into microbial cells and that DNA can be incorporated into their genomes.”
These processes make it difficult to sort coexisting microbes into distinct populations based on their genetic makeup. “If we can’t identify those populations in microbes, we can’t one-to-one apply all this rich ecological and evolutionary theory that has been developed for plants and animals to microbes,” says Polz.
Microbiology graduate student David VanInsberghe then suggested a “reverse ecology” approach that could identify regions of the genome in these newly defined populations that show “selective sweeps” — places where DNA variation is reduced or eliminated, likely as a result of strong natural selection for a particular beneficial genetic variant.
By identifying specific sweeps within populations, and mapping the distribution of these populations, the method can reveal possible adaptations that drive microbes to inhabit a particular environment or host — without any prior knowledge of their environment. When the researchers tested this approach in the gut bacterium Ruminococcus gnavus, they uncovered separate populations of the microbe associated with healthy people and patients with Crohn’s disease.
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