The broom of the system: Tracking soft selective sweeps in bacteria colonizing the gut

ποντίκι / μυς, mouse (Mus musculus) by George Shuklin

Evolution inside this mouse’s gut (and yours) is more complex than you might think.

A growing body of population genetic evidence suggests that adaptive evolutionary change often proceeds via soft selective sweeps, in which beneficial mutations on multiple genetic backgrounds—and potentially at multiple loci—all increase in frequency, but none achieve fixation. This process has been directly tracked in populations of HIV within patients receiving antiretroviral drugs; and now a recent paper in PLOS Genetics finds that soft sweeps are integral in the adaptation of bacteria to the mammalian gut.

João Barroso-Batista and colleagues at the Instituto Gulbenkian de Ciência and Instituto de Tecnologia Química e Biológica in Portugal first treated mice with streptomycin to clear their guts of bacteria, then fed them cultures of Escherichia coli that were genetically uniform—except that half the E. coli cells in the culture had been engineered to produce a blue fluorescent protein, and half had been engineered to produce a yellow fluorescent protein. Any adaptation to the mouse guts would have to occur via new mutation, which might pop up in either a blue or a yellow cell. If a single mutation made that one cell so successful that its descendants entirely dominated the gut, the authors would be able to tell—by checking the color of the host mouse’s poop.

Yes, you read that correctly.

In every case, E. coli sampled from the experimental mice adapted to their hosts’ guts—they out-competed the ancestral strain when both were introduced into new mice at the same time. But in many cases, the adapted populations weren’t uniformly blue or yellow, but a mixture of the two. In the absence of recombination (which occurs more slowly than mutation or selective change in E. coli.) that meant that mutations underlying adaptation had appeared on at least two different genetic backgrounds.

Barroso-Batista et al. dug into the details of that adaptive change by sequencing the genomes of adapted E. coli samples and comparing them to the sequence of the ancestral strain. Multiple loci showed signs of change, but every evolved sample carried mutations in gat, a collection of genes responsible for metabolism of galactitol. Galactitol inhibited the growth of the ancestral strain, but not the evolved samples, and it is present in the mouse gut—so the authors speculate that disabling its metabolism is advantageous in that environment. Crucially, there were many mutations observed that disabled different genes within gat, and these often co-occurred in the same evolving E. coli population.

Clonal interference, caught in the act. Figure 5A from Barroso-Batista et al. (2014).

Clonal interference, caught in the act. Blue or yellow shading indicates fluorescent-labelled genetic background; text labels indicate mutations to genes within gat (A, C, Y, or Z) or other genes. Dashed lines indicate sampling points, with time in days (top) and E. coli generations (bottom). Figure 5A from Barroso-Batista et al. (2014).

Sequencing samples taken at intervals over the course of 24 days allowed the authors to directly visualize this evolving diversity of mutations, as in the figure above. Because there is (probably) not a lot of recombination going on in the course of this adaptive trajectory, different lineages carrying adaptive mutations to the same genes are maintained by classic clonal interference—competition among E. coli lines with effectively equal fitness in the gut environment.

We’re in the midst of a boom in understanding the importance of our relationship to the microbes that live in and on us, and this is a nice addition to that understanding. Particularly, it emphasizes the importance of evolutionary change in the course of establishing our internal microbial community—much as we’d expect to see in the colonization of any new environment.


Barroso-Batista, J., A. Sousa, M. Lourenço, M.-L. Bergman, D. Sobral, J. Demengeot, K. B. Xavier, and I. Gordo. 2014. The first steps of adaptation of Escherichia coli to the gut Are dominated by soft sweeps. PLOS Genetics. 10:e1004182. doi: 10.1371/journal.pgen.1004182.

Hermisson, J., and P. S. Pennings. 2005. Soft sweeps: Molecular population genetics of adaptation from standing genetic variation. Genetics. 169:2335–52. doi: 10.1534/genetics.104.036947.

Messer, P. W., and D. A. Petrov. 2013. Population genomics of rapid adaptation by soft selective sweeps. Trends Ecol. Evol. 28:659–669. doi: 10.1016/j.tree.2013.08.003.

About Jeremy Yoder

Jeremy Yoder is a postdoctoral associate in the Department of Forest and Conservation Sciences at the University of British Columbia. He also blogs at Denim and Tweed, and tweets under the handle @jbyoder.
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