The details in the distributions: why and how to study phenotypic variability

• Variation exists within genetically identical populations raised in nominally identical environments.
• This variation, called ‘phenotypic variability,’ is relevant in medicine and agriculture.
• The frequency, adaptive value and mechanistic basis of phenotypic variability in nature are unknown.
• New experimental and statistical methods allow rigorous analysis of phenotypic variability.

Phenotypic variability is present even when genetic and environmental differences between cells are reduced to the greatest possible extent. For example, genetically identical bacteria display differing levels of resistance to antibiotics, clonal yeast populations demonstrate morphological and growth-rate heterogeneity, and mouse blastomeres from the same embryo have stochastic differences in gene expression. However, the distributions of phenotypes present among isogenic organisms are often overlooked; instead, many studies focus on population aggregates such as the mean. The details of these distributions are relevant to major questions in diverse fields, including the evolution of antimicrobial-drug and chemotherapy resistance. We review emerging experimental and statistical techniques that allow rigorous analysis of phenotypic variability and thereby may lead to advances across the biological sciences.

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