title: A system for studying evolution of life-like virtual organisms.
abstract: BACKGROUND
  Fitness landscapes, the dependences of fitness on the genotype, are of critical importance for the evolution of living beings. Unfortunately, fitness landscapes that are relevant to the evolution of complex biological functions are very poorly known. As a result, the existing theory of evolution is mostly based on postulated fitness landscapes, which diminishes its usefulness. Attempts to deduce fitness landscapes from models of actual biological processes led, so far, to only limited success.
  
  
  RESULTS
  We present a model system for studying the evolution of biological function, which makes it possible to attribute fitness to genotypes in a natural way. The system mimics a very simple cell and takes into account the basic properties of gene regulation and enzyme kinetics. A virtual cell contains only two small molecules, an organic nutrient A and an energy carrier X, and proteins of five types--two transcription factors, two enzymes, and a membrane transporter. The metabolism of the cell consists of importing A from the environment and utilizing it in order to produce X and an unspecified end product. The genome may carry an arbitrary number of genes, each one encoding a protein of one of the five types. Both major mutations that affect whole genes and minor mutations that affect individual characteristics of genes are possible. Fitness is determined by the ability of the cell to maintain homeostasis when its environment changes. The system has been implemented as a computer program, and several numerical experiments have been performed on it. Evolution of the virtual cells usually involves a rapid initial increase of fitness, which eventually slows down, until a fitness plateau is reached. The origin of a wide variety of genetic networks is routinely observed in independent experiments performed under the same conditions. These networks can have different, including very high, levels of complexity and often include large numbers of non-essential genes.
  
  
  CONCLUSIONS
  The described system displays a rich repertoire of biologically sensible behaviors and, thus, can be useful for investigating a number of unresolved issues in evolutionary biology, including evolution of complexity, modularity and redundancy, as well as for studying the general properties of genotype-to-fitness maps.
  
  
  METHODS
  This article was reviewed by Drs. Eugene Koonin, Shamil Sunyaev and Arcady Mushegian.
authors.affiliation: Center for Pharmaceutical Biotechnology, University of Illinois at Chicago, Chicago, IL 60607, USA.
authors.forename: Alex A
authors.initials: AA
authors.lastname: Neyfakh
authors.forename: Natalya N
authors.initials: NN
authors.lastname: Baranova
authors.forename: Lev J
authors.initials: LJ
authors.lastname: Mizrokhi