Phenotypic Plasticity and Effects of Selection on Cell Division Symmetry in Escherichia coli Uttara N. Lele1, Ulfat I. Baig1, Milind G. Watve2* 1 Department of Microbiology, Abasaheb Garware College, Pune, India, 2 Indian Institute of Science, Education, and Research, Pune, India Abstract Aging has been demonstrated in unicellular organisms and is presumably due to asymmetric distribution of damaged proteins and other components during cell division. Whether the asymmetry-induced aging is inevitable or an adaptive and adaptable response is debated. Although asymmetric division leads to aging and death of some cells, it increases the effective growth rate of the population as shown by theoretical and empirical studies. Mathematical models predict on the other hand, that if the cells divide symmetrically, cellular aging may be delayed or absent, growth rate will be reduced but growth yield will increase at optimum repair rates. Therefore in nutritionally dilute (oligotrophic) environments, where growth yield may be more critical for survival, symmetric division may get selected. These predictions have not been empirically tested so far. We report here that Escherichia coli grown in oligotrophic environments had greater morphological and functional symmetry in cell division. Both phenotypic plasticity and genetic selection appeared to shape cell division time asymmetry but plasticity was lost on prolonged selection. Lineages selected on high nutrient concentration showed greater frequency of presumably old or dead cells. Further, there was a negative correlation between cell division time asymmetry and growth yield but there was no significant correlation between asymmetry and growth rate. The results suggest that cellular aging driven by asymmetric division may not be hardwired but shows substantial plasticity as well as evolvability in response to the nutritional environment. Citation: Lele UN, Baig UI, Watve MG (2011) Phenotypic Plasticity and Effects of Selection on Cell Division Symmetry in Escherichia coli. PLoS ONE 6(1): e14516. doi:10.1371/journal.pone.0014516 Editor: Matt Kaeberlein, University of Washington, United States of America Received May 21, 2010; Accepted December 14, 2010; Published January 10, 2011 Copyright: 2011 Lele et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: UL was supported by a junior research fellowship by the Council for Scientific and Industrial Research, India. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: milind@iiserpune.ac.in Introduction Aging is known to occur in bacteria and yeast that divide with morphological asymmetry [1–3]. For species that appear to divide symmetrically, aging was demonstrated relatively recently [4] and is thought to arise from aggregation and asymmetric inheritance of oxidatively damaged proteins [5–9]. In fact, the two cells after division can be viewed as a parent cell and a daughter cell rather than as two sister cells. This gives rise to a population dynamics that is similar to multicellular organisms that show age structured populations. Based on a Leslie Matrix model Watve et al. [10] simulated symmetric and asymmetric division and its effects on population growth. Their model assumed that the efficiency of cellular components declined with age and growth rate of a cell was a function of the relative proportions of new and old components. In asymmetrically dividing cells although a propor- tion of cells accumulated older components and ultimately died, young cells were being continuously generated and therefore the growth rate of the population remained high. On the other hand, in a symmetrically dividing culture, all the cells retained a proportion of older components resulting in slower growth of the entire population. Other studies based on mathematical models agreed on the growth rate advantage of asymmetric division [11– 12]. In the Watve et al [10] model, at an optimum rate of repair the growth yield or biomass conversion efficiency of symmetrically dividing cells was predicted to be higher than asymmetrically dividing ones. Based on the simulation results Watve et al. [10] argued that symmetric division was a better strategy under low nutrient conditions when biomass conversion efficiency would be more critical. On the other hand under a nutritionally rich but highly competitive environment, asymmetrically dividing cells would gain a reproductive advantage. Another critical outcome of the model was that in low nutrient environments repair rates should be higher. Efficient repair systems can give fitness advantages only if the division is symmetric. Asymmetric division strategy on the other hand is unable to make optimum use of the repair mechanisms. The advantage of asymmetric division in increasing the growth rate has been demonstrated experimentally [4,7]. The other prediction of the model, however, remains to be tested. If bacteria are shown to have different cell division asymmetries in different environments it would indicate that asymmetric division and aging may not be inevitable for bacteria but are adaptations for faster growth in a growth supportive and competitive environment. A shift in cell division strategy, if any, may be observable in ecological or evolutionary time. If the cells have phenotypic plasticity, they may change cell division strategies in response to the environment in a short duration. Alternatively optimum cell division symmetry may evolve by prolonged selection in a given environment. Such a change should be observable in evolutionary time. We test here whether the asymmetry in cell division changes in response to the nutritional environment as per the model prediction [10] and whether this happens owing to phenotypic plasticity or genetic selection. PLoS ONE | www.plosone.org 1 January 2011 | Volume 6 | Issue 1 | e14516