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Table 1 Summary of impact of biotic and abiotic environment on diversification in experimental evolution, with parallels in tumor biology

From: Intra-tumor heterogeneity: lessons from microbial evolution and clinical implications

Factors in diversification Effect on diversity Evolutionary theory Observed patterns in oncology References
Biotic     
Mutation A higher mutation rate increases genetic variation and facilitates faster adaptation, with fitness cost as trade-off Genomic instability is an important source of genetic alterations (nucleotide mutations, deletions, amplifications and chromosomal rearrangements) [5, 6, 23, 24]
Interspecific interactions ↑↓ Competitive intereactions may drive diversification under weak selection. Under strong selection, bottlenecks may reduce diversity Tumor cells do interact with their environment, but the role of the microenvironment in driving genetic heterogeneity remains poorly understood [8, 2532]
  ↑↓ Cooperative interactions drive diversification as structured environments mediate interactions between local cells creating heterogeneity across space Tumors that grow at metastatic sites display organ-specific genetic alterations, which might be due to microenvironmental differences [8, 2532]
Intraspecific interactions ↑↓ In a heterogeneous environment, localized interactions (competitive or cooperative) will increase diversity; in an homogenous environment, a single clone will tend to dominate Intra-tumor heterogeneity exists at genotypic and at phenotypic levels (such as quiescent cells, differentiated cells, stem cells), which probably influence each other, in either a cooperative way (for example, generating specific niches) or a competitive way (for example, competition for limited resources or space) [3335]
Individual movement (migration/dispersal) Migrants will encounter different ecological conditions and thus will diverge from their primary population Deep-sequencing data show that metastases do have unique mutations that are not detected in the primary tumor [14, 15, 36, 37]
Abiotic     
Heterogeneity in space A heterogenic environment provides multiple niches Levels of oxygen and nutrients are not uniform throughout a tumor [3841]
Heterogeneity in time Different subclones will be favored over time. A more rapidly changing environment will maintain more subclones A longitudinal study that included untreated CLL patients failed to observe a change in the relative presence of subclones in most cases within the time-frame of the study [42, 43]
Exposure to non-living antagonists Exposure to antagonists tend to create bottlenecks, limiting diversity and favoring only resistant clones Drug treatment can create a bottleneck, selecting the survival of less sensitive clones, thereby decreasing heterogeneity [7, 42, 44, 45]