Biology subjects

Bartlomiej Waclaw

Publications and source records attributed to Bartlomiej Waclaw.

4 recordsLinked to original sources

bioRxiv2016

Beyond the Hypercube: Evolutionary Accessibility of Fitness Landscapes with Realistic Mutational Networks

Evolutionary pathways describe trajectories of biological evolution in the space of different variants of organisms (genotypes). The probability of existence and the number of evolutionary pathways that lead from a given genotype to a better-adapted genotype are important measures of accessibility of local fitness optima and the reproducibility of evolution. Both quantities have been studied in simple mathematical models where genotypes are represented as binary sequences of two types of basic units, and the network of permitted mutations between the genotypes is a hypercube graph. However, it is unclear how these results translate to the biologically relevant case in which genotypes are represented by sequences of more than two units, for example four nucleotides (DNA) or 20 aminoacids (proteins), and the mutational graph is not the hypercube. Here we investigate accessibility of the best-adapted genotype in the general case of K > 2 units. Using computer generated and experimental fitness landscapes we show that accessibility of the global fitness maximum increases with K and can be much higher than for binary sequences. The increase in accessibility comes from the increase in the number of indirect trajectories exploited by evolution for higher K. As one of the consequences, the fraction of genotypes that are accessible increases by three orders of magnitude when the number of units K increases from 2 to 16 for landscapes of size N ~ 106 genotypes. This suggests that evolution can follow many different trajectories on such landscapes and the reconstruction of evolutionary pathways from experimental data might be an extremely difficult task.

Evolutionary Biology↗

bioRxiv2016

Allele Surfing Promotes Microbial Adaptation from Standing Variation

The coupling of ecology and evolution during range expansions enables mutations to establish at expanding range margins and reach high frequencies. This phenomenon, called allele surfing, is thought to have caused revolutions in the gene pool of many species, most evidently in microbial communities. It has remained unclear, however, under which conditions allele surfing promotes or hinders adaptation. Here, using microbial experiments and simulations, we show that, starting with standing adaptive variation, range expansions generate a larger increase in mean fitness than spatially uniform population expansions. The adaptation gain results from soft selective sweeps emerging from surfing beneficial mutations. The rate of these surfing events is shown to sensitively depend on the strength of genetic drift, which varies among strains and environmental conditions. More generally, allele surfing promotes the rate of adaptation per biomass produced, which could help developing biofilms and other resource-limited populations to cope with environmental challenges.

Evolutionary Biology↗

bioRxiv2016

Phenotypic switching can speed up biological evolution of microbes

Stochastic phenotype switching has been suggested to play a beneficial role in microbial populations by leading to the division of labour among cells, or ensuring that at least some of the population survives an unexpected change in environmental conditions. Here we use a computational model to investigate an alternative possible function of stochastic phenotype switching - as a way to adapt more quickly even in a static environment. We show that when a genetic mutation causes a population to become less fit, switching to an alternative phenotype with higher fitness (growth rate) may give the population enough time to develop compensatory mutations that increase the fitness again. The possibility of switching phenotypes can reduce the time to adaptation by orders of magnitude if the \"fitness valley\" caused by the deleterious mutation is deep enough. Our work has important implications for the emergence of antibiotic-resistant bacteria. In line with recent experimental findings we hypothesise that switching to a slower growing but less sensitive phenotype helps bacteria to develop resistance by exploring a larger set of beneficial mutations while avoiding deleterious ones.

Evolutionary Biology↗

bioRxiv2015

Spatial model predicts dispersal and cell turnover cause reduced intra-tumor heterogeneity

Most cancers in humans are large, measuring centimeters in diameter, composed of many billions of cells. An equivalent mass of normal cells would be highly heterogeneous as a result of the mutations that occur during each cell division. What is remarkable about cancers is their homogeneity - virtually every neoplastic cell within a large cancer contains the same core set of genetic alterations, with heterogeneity confined to mutations that have emerged after the last clonal expansions. How such clones expand within the spatially-constrained three dimensional architecture of a tumor, and come to dominate a large, pre-existing lesion, has never been explained. We here describe a model for tumor evolution that shows how short-range migration and cell turnover can account for rapid cell mixing inside the tumor. With it, we show that even a small selective advantage of a single cell within a large tumor allows the descendants of that cell to replace the precursor mass in a clinically relevant time frame. We also demonstrate that the same mechanisms can be responsible for the rapid onset of resistance to chemotherapy. Our model not only provides novel insights into spatial and temporal aspects of tumor growth but also suggests that targeting short range cellular migratory activity could have dramatic effects on tumor growth rates.

Cancer Biology↗