Evolution of the AMP-Activated Protein Kinase Controlled Gene Regulatory Network

Abstract

Alterations in gene regulation are considered major driving forces in divergent evolution. This is reflected in different species by the variable architecture of regulatory networks controlling highly conserved metabolic pathways. While many regulatory proteins are surprisingly conserved their wiring has evolved more rapidly. This project focuses on the adaptation to nutrient limitation, which requires the activation of the conserved AMP-activated protein kinase (AMPK alias Snf1 in yeast) and its downstream effectors. The goal is to uncover basic principles of adaptation and steps in the evolutionary process associated with regulatory network rearrangement. This requires improving the prediction of gene regulation based experimental data, DNA sequence information and information theory. In this project Context Tree (CT) models and Parsimonious Context Tree (PCT) models and the corresponding algorithms for extended Context Tree Maximization (CTM) and extended Parsimonious Context Tree Maximization (PCTM) are derived, implemented, and applied. Computational predictions and experimental validation will establish an iterative cycle to improve algorithms in each cycle leading to a growing set of experimentally verified and falsified predictions, finally allowing a deeper understanding of the evolution of the transcriptional regulatory network controlling energy metabolism, one of the most fundamental processes conserved across all kingdoms of life.