Biology subjects

Guet, C. C.

Publications and source records attributed to Guet, C. C..

3 recordsLinked to original sources

bioRxiv2021

Local genetic context shapes the function of a gene regulatory network

Gene expression levels are influenced by multiple coexisting molecular mechanisms. Some of these interactions, such as those of transcription factors and promoters have been studied extensively. However, predicting phenotypes of gene regulatory networks remains a major challenge. Here, we use a well-defined synthetic gene regulatory network to study how network phenotypes depend on local genetic context, i.e. the genetic neighborhood of a transcription factor and its relative position. We show that one gene regulatory network with fixed topology can display not only quantitatively but also qualitatively different phenotypes, depending solely on the local genetic context of its components. Our results demonstrate that changes in local genetic context can place a single transcriptional unit within two separate regulons without the need for complex regulatory sequences. We propose that relative order of individual transcriptional units, with its potential for combinatorial complexity, plays an important role in shaping phenotypes of gene regulatory networks.

molecular biology↗

bioRxiv2020

Structure and Evolution of Constitutive Bacterial Promoters

Predicting gene expression levels from any DNA sequence is a major challenge in biology. Using libraries with >25,000 random mutants, we developed a biophysical model that accounts for major features of {sigma}70-binding bacterial promoters to accurately predict constitutive gene expression levels of any sequence. We experimentally and theoretically estimated that 10-20% of random sequences lead to expression and 82% of non-expressing sequences are one point mutation away from a functional promoter. Generating expression from random sequences is pervasive, such that selection acts against {sigma}70-RNA polymerase binding sites even within inter-genic, promoter-containing regions. The pervasiveness of {sigma}70- binding sites, which arises from the structural features of promoters captured by our biophysical model, implies that their emergence is unlikely the limiting step in gene regulatory evolution.

evolutionary biology↗

bioRxiv2020

Population dynamics of decision making in temperate bacteriophages

Due to their ability to choose between lysis and lysogeny, temperate bacteriophages represent a classic model system to study the molecular basis of decision making. The coinfection of individual bacteria by multiple, genetically identical phages is known to alter the infection outcome and favor lysogeny over lytic development. However, it is not clear what role the ability of individual phages to sense and respond to coinfections plays in the phage-host infection dynamics at the population level. To address this question, we developed a full-stochastic model to capture the interaction dynamics between billions of bacteria and phages with single-cell and -phage resolution. While, at the level of individual bacteria, the probability of coinfections depends mainly on the phage concentration at the time of infection, the average number of coinfections at the population level is primarily determined by the relative growth rate of phage. Because the maximum attainable phage growth rate is constrained by basic life history parameters, the average number of coinfections has an upper bound of around two. However, for a broad range of conditions, the average number of coinfections stays well below this value. Consequently, we find that coinfections provide only very limited information to individual phages about the state of the infection at the population level. Nevertheless, this information can still provide a strong competitive advantage for phages that base fate decisions on the number of coinfections.

evolutionary biology↗