Theoretical Investigation Of Intrinsic Fluctuation In Gene Regulation Network

With the dramatic advances in the science and technology fields in the 21st century, the flurry of genomic research has led to detailed lists of the genes. However,there are still problems to be solved in biological field. For examples, Research of dynamic properties in complex gene regulation network and multi-complex biological systems become hot spot in the next step of genomic study in life science. As McAdams said, gene expression is'noise's business'. These years much attraction is imposed on studying resources and properties of intrinsic fluctuation. With great breakthroughs in experimental and theoretical studies in gene network, people have better understanding of noise and discuss the noise resource, noise properties and noise functions, etc. Recently, Paulsson discussed theoretically and made a summary of noise in gene regulation networks, while Elowitz developed a two reporter assay to measure the impact of both gene-intrinsic and gene-extrinsic noise on population heterogeneity directly, which promote the understanding of stochasticity in gene expression. However, we lack disciplinary and systematic understanding of the relationship between topology of gene networks and fluctuation character of products. Hence, it is very meaningful to analyze the properties in defined structure of complex gene regulation network and then to deduce the structure from the fluctuation.Many real biological networks contain significantly recurring wiring patterns termed"network motifs"and the component within one motif does not connect to that of other one directly. One of the most well-known and important motifs appearing in gene networks is the feed forward loop (FFL) which contains three genes X,Y and Z . Protein-X synthesized from gene-X regulates the expression of gene-Y and Z, and protein-X and protein-Y also jointly regulate the expression of gene Z. Each of the three transcriptional regulatory interactions in a FFL has either positive sign (activation) or negative sign (repression), and thus the motif can be in eight possible configurations which are of two types: coherent and incoherent. In a coherent (incoherent) FFL, the sign of the direct regulation path from X to Z is the same as (different from) the overall sign of the indirect regulation path via Y.Recently, Lipan and Wong (PNAS 2005) presented a theory by which the structure of a genetic network can be uncovered by studying its response to external stimuli. The use of an oscillatory signal is proved to be more advantageous than a step or impulse signal. The scheme was based on a new phenomenon, called fluctuation resonance (FR). For single gene expression process, fluctuation of the protein number would be also periodic in time if the transcription is subject to external periodic signal. FR tells that the deviation from Poisson process would reach a clear-cut maximum when the frequency of the external signal is at an intermediate value. In the present work, we consider a stochastic genetic FFL, with an oscillatory signal stimulating the gene X, with particular attention paid to the FR behaviors of all the three genes. We find that the response of the gene Z clearly reflects the coherent properties of the system, indicating that one could use small external signal to help identify the regulatory structure of an unknown FFL in complex gene networks.