Stress-Induced Mutagenesis and Complex Adaptation

Yoav Ram, Lilach Hadany

doi: http://dx.doi.org/10.1101/007096

 

Abstract:

Because mutations are mostly deleterious, mutation rates should be reduced by natural selection. However, mutations also provide the raw material for adaptation. Therefore, evolutionary theory suggests that the mutation rate must balance between adaptability - the ability to adapt - and adaptedness - the ability to remain adapted. We model an asexual population crossing a fitness valley and analyze the rate of complex adaptation with and without stress-induced mutagenesis - the increase of mutation rates in response to stress or maladaptation. We show that stress-induced mutagenesis increases the rate of complex adaptation without reducing the population mean fitness, thus breaking the evolutionary trade-off between adaptability and adaptedness. Our theoretical results support the hypothesis that stress-induced mutagenesis promotes adaptation and provide quantitative predictions of the rate of complex adaptation with different mutational strategies.

 

Link: http://www.biorxiv.org/content/early/2014/07/21/007096.abstract?%3Fcollection=

 

Keywords: Adaptation, stress, evolution

Not strictly cancer but the topic is very relevant to many of us trying to understand the emergence of invasiveness.

The Role of Migration in the Evolution of Phenotypic Switching

Oana Carja, Robert E Furrow, Marc W Feldman

 

Stochastic switching is an example of phenotypic bet-hedging, where an individual can switch between different phenotypic states in a fluctuating environment. Although the evolution of stochastic switching has been studied when the environment varies temporally, there has been little theoretical work on the evolution of phenotypic switching under both spatially and temporally fluctuating selection pressures. Here we use a population genetic model to explore the interaction of temporal and spatial variation in the evolutionary dynamics of phenotypic switching. We find that spatial variation in selection is important; when selection pressures are similar across space, migration can decrease the rate of switching, but when selection pressures differ spatially, increasing migration between demes can facilitate the evolution of higher rates of switching. These results may help explain the diverse array of non-genetic contributions to phenotypic variability and phenotypic inheritance observed in both wild and experimental populations.

 

Source: bioRxiv

 

Investigating the development of chemotherapeutic drug resistance in cancer: A multiscale computational study

Investigating the development of chemotherapeutic drug resistance in cancer: A multiscale computational study

 By: Gibin G Powathil, Mark AJ Chaplain, Maciej Swat

Chemotherapy is one of the most important therapeutic options used to treat human cancers, either alone or in combination with radiation therapy and surgery. Recent studies have indicated that intra-tumoural heterogeneity has a significant role in driving resistance to chemotherapy in many human malignancies. Multiple factors including the internal cell-cycle dynamics and the external microenvironement contribute to the intra-tumoural heterogeneity. In this paper we present a hybrid, multiscale, individual-based mathematical model, incorporating internal cell-cycle dynamics and changes in oxygen concentration, to study the effects of delivery of several different chemotherapeutic drugs on the heterogeneous subpopulations of cancer cells with varying cell-cycle dynamics. The computational simulation results from the multiscale model are in good agreement with available experimental data and support the hypothesis that slow-cycling sub-populations of tumour cells within a growing tumour mass can induce drug resistance to chemotherapy and thus the use of conventional chemotherapy may actually result in the emergence of dominant, therapy-resistant, slow-cycling subpopulations of tumour cells. Our results indicate that the appearance of this chemotherapeutic resistance is mainly due to the inability of the administered drug to target all cancer cells irrespective of the stage in the cell-cycle they are in i.e. most chemotherapeutic drugs target cells in a particular phase/phases of the cell-cycle, and hence always spare some cancer cells that are not in the targeted cell-cycle phase/phases. The results also suggest that this cell-cycle-mediated drug resistance may be overcome by using multiple doses of cell-cycle, phase-specific chemotherapy that targets cells in all phases and its appropriate sequencing and scheduling.   

http://arxiv.org/abs/1407.0865