Natural Biased Coin Encoded in the Genome Determines Cell Strategy

Abstract

Decision making at a cellular level determines different fates for isogenic cells. However, it is not yet clear how rational decisions are encoded in the genome, how they are transmitted to their offspring, and whether they evolve and become optimized throughout generations. In this paper, we use a game theoretic approach to explain how rational decisions are made in the presence of cooperators and competitors. Our results suggest the existence of an internal switch that operates as a biased coin. The biased coin is, in fact, a biochemical bistable network of interacting genes that can flip to one of its stable states in response to different environmental stimuli. We present a framework to describe how the positions of attractors in such a gene regulatory network correspond to the behavior of a rational player in a competing environment. We evaluate our model by considering lysis/lysogeny decision making of bacteriophage lambda in E. coli.

Heterogeneity in phage induction enables the survival of the lysogenic population

“…Stx phage induction might also be required when cells are being threatened by the immune system, as shown in previous studies indicating induction of Stx phages by neutrophils (Wagner et al ., ). In addition to the stochastic switch in the absence of stress conditions, cells would need mechanisms to eliminate the noise and bias the switch towards the stabilization of their state if necessary (Dorri et al ., ) because the progress of infection depends on their ability to colonize, to compete against other bacteria and to deal with different stressors. Because activation of the lytic cycle leads to a higher Stx expression, therapies based on the maintenance of the lysogeny in STEC could help avoid some of the most threatening consequences of STEC infection, such as the development of haemolytic uremic syndrome.…”