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Affiliated institutions: Arizona State University

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Description: Previous work has established that the number of ribosomes in a cell represents the primary constraint on how fast cells can grow and divide. This constraint, called a “growth law” is apparent across the tree of life. It is obvious why the number of ribosomes sets a lower limit on how fast cells can make more cells: ribosomes are required to make all the cellular components. But there may exist other constraints that prevent cells from reaching their growth potential even when enough ribosomes are present. These additional constraints may have been missed by previous work because that work largely focuses on cells growing in steady nutrient levels in chemostats. These experiments may miss growth-limiting parameters that dictate the limits of cellular evolution because natural populations of cells are prone to experience feast and famine scenarios. Here, we explore the extent to which ribosome content predicts growth rate in conditions where microbial cells are slowly consuming all available nutrients. It is well known that microbial cell populations “bet hedge” to contend with famine, whereby different cells deploy different strategies in response to nutrient depletion. Therefore, we use a single cell approach to measure ribosomal content. Though we confirm that the growth law holds true for populations of cells that are depleting their nutrients, we find that ribosomal content alone is a poor predictor of the growth rate of single cells. We observe enormous variance in the ribosomal content from cell to cell, and opposite expectations, this variance decreases with decreasing nutrient availability. By analyzing the full transcriptional profiles of cells with different ribosomal content and different growth rates, we begin to reveal additional constraints on making a cell, for example, the degree to which resources are divested towards stress responses. This study, and the novel biology we learned, were made possible because we utilized a new single-cell RNA seq approach that allows sampling the transcriptomes of thousands of microbial cells. We applied this approach to cells of two different microbes, the eukaryotic yeast, S. cerevisiae, and the prokaryote, B. subtilis, both of which appear to grow at rates dictated by constraints in addition to ribosome number.

License: CC0 1.0 Universal

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