Research Paper Volume 6, Issue 12 pp 1033—1048

Figure 7. A schemata of a phenotype's fitness/survival determination in a complex environment. (A) An illustration of the Shelford's Law of Tolerance: species survival decreases with a change in an environmental factor from the optimum towards its extrema within the species' tolerance range; selection drives adaptation of a species towards best survival optima (occupied by phenotype A in panel A). (B) Body fitness decline in humans and mammals is delayed until the post-reproductive period when selection for high fitness of the body is relaxed; at the animal population level microenvironment integrity is not supported by selection as age advances into the post-reproductive period and cells do not evolve to optimally perform in the altered microenvironment. (C) An example of cell fitness determination within a hypothetical bifactorial tissue microenvironment. The normal cell phenotype evolves for optimal performance at the animal population level, and thus the probability of somatic mutations that enhance cell performance is reduced. The evolved (“normal”) and mutant cell phenotypes have different degrees of adaptation to microenvironmental factors A and B (solid lines connecting to the right “adaptation” axis); following the Sprengel-Liebig Law of the Minimum, fitness of both phenotypes is limited by the factor each phenotype is least adapted to (dashed lines connecting to the left “fitness” axis). (D) An altered microenvironment of aging post-reproductive tissues (factor A and B intensities have changed). Selection at the animal population level is relaxed and neither of the cell phenotypes have evolved to an aged microenvironment (both are out of optima), but the fitness of the mutant phenotype may become higher in the altered microenvironment. (E) A phenotypically homogenous population of cells will decline in fitness in a degraded microenvironment, revealing the microenvironment's uniform component that affects fitness. (F) Phenotypic diversity creates fitness differential in the cell pool. In a degraded microenvironment relative fitness of cells may change and initially disadvantageous mutant phenotypes may gain in fitness relative to others (red cell in panel F) and vice versa (green cell), revealing the microenvironment's stochastic component affecting fitness independently of the initial fitness distribution.