Resource competition in Three-gene-motif & Emergence of Feed-forward response: A Spatiotemporal Study

Abstract: Feed-forward dynamics, which is well-known to have several important implications in nonlinear dynamical systems, frequently occurs in gene expression motifs, and has been well explored experimentally and mathematically. However, dependency of the components of a genetic circuit upon its host, due to the requirement for resources like ribosome, ATP, transcription factors, tRNA, etc., and related effects are of utmost importance, which is commonly ignored in mathematical models. In a resource-limited environment, two apparently unconnected genes can compete for resources for their respective expression and may exhibit indirect regulatory connection; an emergent response thus arises in the system completely because of resource competition. In this work, we have shown how the responses of the feed-forward loop (FFL), a well-studied regulatory genetic motif, can be recreated considering the resource competition in a three-gene pathway. Exploring the genetic system with temporal as well as spatiotemporal stability analysis, interesting transient and steady-state responses have been observed. The genetic motifs explored in this paper show many of the characteristic features of the conventional FFL structure, like response delay and pulse generation. Most interestingly, in a two-dimensional cellular arrangement, characteristic pattern formation under a concentration gradient of input signals have also been observed. This study pinpoints a larger area of research and exploration in synthetic and cellular systems, which will reveal novel controlling ideas and unique behavioral changes in the system for its context dependencies.