Emergent evolutionary forces in spatial models of microbial growth in the human gut microbiota

Abstract

The genetic composition of the gut microbiota is constantly reshaped by ecological and evolutionary forces. These strain-level dynamics can be challenging to understand because they emerge from complex spatial growth processes that take place within a host. Here we introduce a mathematical framework to predict how stochastic evolutionary forces emerge from simple models of microbial growth in the intestinal lumen. Our framework shows how fluid flow and longitudinal variation in growth rate combine to shape the frequencies of genetic variants in sequenced fecal samples, yielding analytical expressions for the effective generation times, selection coefficients, and rates of genetic drift. We find that the emergent evolutionary dynamics can often be captured by well-mixed models that lack explicit spatial structure, even when there is substantial spatial variation in species-level composition. By applying these results to the human colon, we find that continuous fluid flow is unlikely to create sufficient bottlenecks to allow large fluctuations in mutant frequencies within a host, while the effective generation times may be significantly shorter than expected from traditional average growth rate estimates. Our results provide a starting point for quantifying genetic turnover in the gut microbiota, and may be relevant for other microbial ecosystems where unidirectional fluid flow plays an important role.

Hydrodynamic flow and concentration gradients in the gut enhance neutral bacterial diversity

“…This rate can also be expressed as the active population size divided by the minimal replication time τ rep , because bacteria in the active population reproduce at rates close to the maximal one. Thus, the ratio of active to total population size is equal to the ratio of minimal replication time to renewal time, which, as discussed in previous section, can be as small as 20/(24 × 60) = 1.4 × 10 −2 , and is likely to be of order 0.1 (also consistent with [64]). In addition, fixation of a mutant occurs within a strain.…”

“…Note. While this manuscript was in revision, an independent and complementary study [64] was released on BioRxiv.…”

Dynamics of bacterial recombination in the human gut microbiome

“…Many gut commensals are known to engage in conjugative transfer, both in vitro and in vivo [77]. However, the time required for bacterial conjugation carries a substantial opportunity cost in the high growth regimes of the large intestine, and would need to be ameliorated by a corresponding fitness benefit or residence in a privileged spatial location [78]. Moreover, we observe little correlation between the overall rates of recombination in different species and their frequency of apparent multi-colonization (Fig.…”

“…3D range from 0.01 – 1, with most species clustering near r/μ ~0.1. Using estimates of the remaining parameters from the existing literature [ N ~ 10 13 – 10 14 [95], μ ~ 10 −10 – 10 −9 [96], L ~ 10 6.5 [97], Δ t ~ 1 – 10 [78, 98]], we expect that a moderately abundant species ( f ~ 3–30%) will produce anywhere from 10 6 to 10 12 recombinant offspring each day.…”

A macroecological perspective on genetic diversity in the human gut microbiome

“…Hundreds to thousands of species continually reproduce in a typical host, dynamics that culminate in the acquisition of ∼ 10 9 de novo mutations each day [1]. Due to the comparatively brief generation time of microbes in the human gut [2], those mutations that are beneficial can rapidly fix on a timescale of days to months [1,[3][4][5][6][7][8]. Such evolutionary dynamics have the capacity to alter the genetic composition of a species within a given host.…”