How the tortoise beats the hare: Slow and steady adaptation in structured populations suggests a rugged fitness landscape in bacteria

Abstract In the context of Wright’s adaptive landscape, genetic epistasis can yield a multipeaked or “rugged” topography. In an unstructured population, a lineage with selective access to multiple peaks is expected to rapidly fix on one, which may not be the highest peak. Contrarily, beneficial mutations in a population with spatially restricted migration take longer to fix, allowing distant parts of the population to explore the landscape semi-independently. Such a population can simultaneous discover multiple peaks and the genotype at the highest discovered peak is expected to fix eventually. Thus, structured populations sacrifice initial speed of adaptation for breadth of search. As in the Tortoise-Hare fable, the structured population (Tortoise) starts relatively slow, but eventually surpasses the unstructured population (Hare) in average fitness. In contrast, on single-peak landscapes (e.g., systems lacking epistasis), all uphill paths converge. Given such “smooth” topography, breadth of search is devalued, and a structured population only lags behind an unstructured population in average fitness (ultimately converging). Thus, the Tortoise-Hare pattern is an indicator of ruggedness. After verifying these predictions in simulated populations where ruggedness is manipulable, we then explore average fitness in metapopulations of Escherichia coli. Consistent with a rugged landscape topography, we find a Tortoise-Hare pattern. Further, we find that structured populations accumulate more mutations, suggesting that distant peaks are higher. This approach can be used to unveil landscape topography in other systems, and we discuss its application for antibiotic resistance, engineering problems, and elements of Wright’s Shifting Balance Process. Significance Statement: Adaptive landscapes are a way of describing how mutations interact with each other to produce fitness. If an adaptive landscape is rugged, organisms achieve higher fitness with more difficulty because the mutations to reach high fitness genotypes may not be always beneficial. By evolving populations of Escherichia coli with different degrees of spatial structure, we identified a Tortoise-Hare pattern, where structured populations were initially slower, but overtook less structured populations in mean fitness. These results, combined with genetic sequencing and computational simulation, indicate this bacterial adaptive landscape is rugged. Our findings address one of the most enduring questions in evolutionary biology, in addition to, providing insight into how evolution may influence medicine and engineering.