Biology subjects

Lindner, A. B.

Publications and source records attributed to Lindner, A. B..

2 recordsLinked to original sources

bioRxiv2018

Temporal scaling of ageing as an adaptive strategy of Escherichia coli

Natural selection has long been hypothesised to shape ageing patterns, but whether and how ageing contributes to life-history evolution remains elusive. The complexity of various ageing-associated molecular mechanisms and their inherent stochasticity hinder reductionist approaches to the understanding of functional senescence, i.e. reduced fecundity and increased mortality. Recent bio-demographic work demonstrated that high-precision statistics of life-history traits such as mortality rates could be used phenomenologically to understand the ageing process. We adopted this approach to study cellular senescence in growth-arrested E. coli cells, where damages to functional macromolecules are no longer diluted by fast de novo biosynthesis. We acquired high-quality longitudinal physiological and life history data of large environmentally controlled clonal E. coli populations at single-cell resolution, using custom-designed microfluidic devices coupled to time-lapse microscopy. We show that E. coli lifespan distributions follow the Gompertz law of mortality, a century-old actuarial observation of human populations, despite developmental, cellular and genetic differences between bacteria and metazoan organisms. Measuring the shape of the hazard functions allowed us to disentangle quantitatively the demographic effects of ageing, which accumulate with time, from age-independent genetic longevity-modulating interventions. A pathway controlling cellular maintenance, the general stress response, not only promotes longevity but also temporally scales the whole distribution by reducing ageing rate. We further show that E. coli, constrained by the amount of total biosynthesis, adapt to their natural feast-or-famine lifestyle by modulating the amount of maintenance investment, rendering ageing rate a highly evolvable life-history trait.

evolutionary biology↗

bioRxiv2018

Systematic detection of amino acid substitutions in proteome reveals a mechanistic basis of ribosome errors

Translation errors limit the accuracy of information transmission from DNA to proteins. Selective pressures shape the way cells produce their proteins: the translation machinery and the mRNA sequences it decodes co-evolved to ensure that translation proceeds fast and accurately in a wide range of environmental conditions. Our understanding of the causes of amino acid misincorporations and of their effect on the evolution of protein sequences is largely hindered by the lack of experimental methods to observe errors at the full proteome level. Here, we systematically detect and quantify errors in entire proteomes from mass spectrometry data. Following HPLC MS-MS data acquisition, we identify E. coli and S. cerevisiae peptides whose mass and fragment ion spectrum are consistent with that of a peptide bearing a single amino acid substitution, and verify that such spectrum cannot result from a post-translational modification. Our analyses confirm that most substitutions occur due to codon-to-anticodon mispairing within the ribosome. Patterns of errors due to mispairing were similar in bacteria and yeast, suggesting that the error spectrum is chemically constrained. Treating E. coli cells with a drug known to affect ribosomal proofreading increased the error rates due to mispairing at the wobble codon position. Starving bacteria for serine resulted in specific patterns of substitutions reflecting the amino acid deficiency. Overall, translation errors tend to occur at positions that are less evolutionarily conserved, and that minimally affect protein energetic stability, indicating that they are selected against. Genome wide ribosome density data suggest that errors occur at sites where ribosome velocity is relatively high, supporting the notion of a trade-off between speed and accuracy as predicted by proofreading theories. Together our results reveal a mechanistic basis for ribosome errors in translation.

systems biology↗