1. Howard Hughes Medical Institute and Division of Biology and Department of Applied Physics, California Institute of Technology, Pasadena, California 91125, USA
2. Department of Microbiology and Immunology, Temple University School of Medicine, 3400 North Broad Street, Philadelphia, Pennsylvania 19140, USA
3. Department of Microbiology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
4. These authors contributed equally to this work.

Correspondence to: Michael B. Elowitz¹ Correspondence and requests for materials should be addressed to M.B.E. (Email: melowitz@caltech.edu).

Abstract

Development normally occurs similarly in all individuals within an isogenic population, but mutations often affect the fates of individual organisms differently^{1, 2, 3, 4}. This phenomenon, known as partial penetrance, has been observed in diverse developmental systems. However, it remains unclear how the underlying genetic network specifies the set of possible alternative fates and how the relative frequencies of these fates evolve^{5, 6, 7, 8}. Here we identify a stochastic cell fate determination process that operates in Bacillus subtilis sporulation mutants and show how it allows genetic control of the penetrance of multiple fates. Mutations in an intercompartmental signalling process generate a set of discrete alternative fates not observed in wild-type cells, including rare formation of two viable 'twin' spores, rather than one within a single cell. By genetically modulating chromosome replication and septation, we can systematically tune the penetrance of each mutant fate. Furthermore, signalling and replication perturbations synergize to significantly increase the penetrance of twin sporulation. These results suggest a potential pathway for developmental evolution between monosporulation and twin sporulation through states of intermediate twin penetrance. Furthermore, time-lapse microscopy of twin sporulation in wild-type Clostridium oceanicum shows a strong resemblance to twin sporulation in these B. subtilis mutants^{9, 10}. Together the results suggest that noise can facilitate developmental evolution by enabling the initial expression of discrete morphological traits at low penetrance, and allowing their stabilization by gradual adjustment of genetic parameters.

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