Implementing Arithmetic and Other Analytic Operations by Transcriptional Regulation

Abstract

The transcriptional regulatory machinery of a gene can be viewed as a computational device, with transcription factor concentrations as inputs and expression level as the output. This view begs the question: what kinds of computations are possible? We show that different parameterizations of a simple chemical kinetic model of transcriptional regulation are able to approximate all four standard arithmetic operations: addition, subtraction, multiplication, and division, as well as various equality and inequality operations. This contrasts with other studies that emphasize logical or digital notions of computation in biological networks. We analyze the accuracy and precision of these approximations, showing that they depend on different sets of parameters, and are thus independently tunable. We demonstrate that networks of these ''arithmetic'' genes can be combined to accomplish yet more complicated computations by designing and simulating a network that detects statistically significant elevations in a time-varying signal. We also consider the much more general problem of approximating analytic functions, showing that this can be achieved by allowing multiple transcription factor binding sites on the promoter. These observations are important for the interpretation of naturally occurring networks and imply new possibilities for the design of synthetic networks.

A Combinatorial Code for Pattern Formation in Drosophila Oogenesis

“…In addition to Boolean logic, developmental cis-regulatory modules and systems for postranscriptional control of gene expression can perform analog operations, leading to multiple nonzero levels of output (Yuh et al, 1998; Davidson, 2001; Buchler et al, 2003; Longabaugh et al, 2005; Istrail et al, 2007; Cory and Perkins, 2008). Consider a module that adds the two binary inputs, shaped as the primitives (Figure 2D).…”