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Beneficial mutations that arise in an evolving asexual population may compete or interact in ways that alter the overall rate of adaptation through mechanisms such as clonal or functional interference. The application of multiple selective pressures simultaneously may allow for a greater number of adaptive mutations, increasing the opportunities for competition between selectively advantageous alterations, and thereby reducing the rate of adaptation. We evolved a strain of Saccharomyces cerevisiae that could not produce its own histidine or uracil for ~500 generations under one or three selective pressures: limitation of the concentration of glucose, histidine, and/or uracil in the media. The rate of adaptation was obtained by measuring evolved relative fitness using competition assays. Populations evolved under a single selective pressure showed a statistically significant increase in fitness on those pressures relative to the ancestral strain, but the populations evolved on all three pressures did not show a statistically significant increase in fitness over the ancestral strain on any single pressure. Simultaneously limiting three essential nutrients for a population of S. cerevisiae effectively slows the rate of evolution on any one of the three selective pressures applied, relative to the single selective pressure cases. We identify possible mechanisms for fitness changes seen between populations evolved on one or three limiting nutrient pressures by high‐throughput sequencing. Adding multiple selective pressures to evolving disease like cancer and infectious diseases could reduce the rate of adaptation and thereby may slow disease progression, prolong drug efficacy and prevent deaths. [ABSTRACT FROM AUTHOR]

If the occurrence of cancer is the result of a random lottery among cells, then body mass, a surrogate for cells number, should predict cancer incidence. Despite some support in humans, this assertion does not hold over the range of different natural animal species where cancer incidence is known. Explaining the so-called 'Peto's paradox' is likely to increase our understanding of how cancer defense mechanisms are shaped by natural selection. Here, we study how body mass may affect the evolutionary dynamics of tumor suppressor gene (TSG) inactivation and oncogene activation in natural animal species. We show that the rate of TSG inactivation should evolve to lower values along a gradient of body mass in a nonlinear manner, having a threshold beyond which benefits to adaptive traits cannot overcome their costs. We also show that oncogenes may be frequently activated within populations of large organisms. We then propose experimental settings that can be employed to identify protection mechanisms against cancer. We finally highlight fundamental species traits that natural selection should favor against carcinogenesis. We conclude on the necessity of comparing genomes between populations of a single species or genomes between species to better understand how evolution has molded protective mechanisms against cancer development and associated mortality. [ABSTRACT FROM AUTHOR]

Contrary to conventional views that assume all cells in a neoplasm can propagate the tumor, the cancer stem cell hypothesis posits that only a fraction of the cells (the cancer stem cells) can act as tumor-propagating cells, while most of the tumor is composed of cells with limited replication potential. Here, we offer an evolutionary approach to this controversy. We used several evolutionary, computational models to investigate cancer cell dynamics and conditions consistent with the stem cell hypothesis. Our models predict that if selection acts at the cell level, neoplasms should be primarily comprised of cancer stem cells, in contrast to experimental data indicating that neoplasms contain large fractions of cancer nonstem cells. We explore several solutions explaining the paradoxical existence of cancer nonstem cells in neoplasms, including the possibility that selection acts at the level of multicellular proliferative units. [ABSTRACT FROM AUTHOR]