Pre-Existing Variation Controls the Lysis-Lysogeny Decision in Phage Lambda Infection

Francois St-Pierre & Drew Endy (MIT)

Abstract

Organismal development is characterized by considerable variation in the fate of individual cells: some cells die while surviving cells differentiate into distinct cell types. Cell fate can be determined by the genetic material, developmental history and local environment of individual cells. However, cell fates are not always predictable. For example, the lysis-lysogeny decision of bacteriophage lambda is considered a paradigm for how chance events drive individual cell fates. Upon infection of Escherichia coli, lambda typically follows one of two mutually exclusive developmental pathways, lytic growth or lysogeny. Genetically identical cells grown in the same environment, each infected with a single phage particle, can produce both outcomes: some cells lyse while others become lysogens. A detailed quantitative model of lambda infection supports the hypothesis that spontaneous biochemical kinetic noise during infection is responsible for observed heterogeneity in cell fate. In contrast with this model, here we show that phenotypic variation present prior to infection controls the lambda lysis-lysogeny decision. Specifically, variation in cell volume can be used to predict cell fate: small cells tend to produce lysogens while larger cells favor lytic growth. Preexisting phenotypic variability not attributed to environmental, lineage or genetic differences may affect the outcome of other cell fate decisions, such as those controlling stem cell or animal development, retroviral infection, drug resistance and cancer.

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