Network-dosage compensation topologies as recurrent network motifs in natural gene networks

Global noise in gene expression and chromosome duplication during cell-cycle progression cause inevitable fluctuations in the effective number of copies of gene networks in cells. These indirect and direct alterations of network copy numbers have the potential to change the output or activity of a gene network. For networks whose specific activity levels are crucial for optimally maintaining cellular functions, cells need to implement mechanisms to robustly compensate the effects of network dosage fluctuations.

Here, we determine the necessary conditions for generalized N-component gene networks to be network-dosage compensated and show that the compensation mechanism can robustly operate over large ranges of gene expression levels. Furthermore, we show that the conditions that are necessary for network-dosage compensation are also sufficient. Finally, using genome-wide protein-DNA and protein-protein interaction data, we search the yeast genome for the abundance of specific dosage-compensation motifs and show that a substantial percentage of the natural networks identified contain at least one dosage-compensation motif.

Our results strengthen the hypothesis that the special network topologies that are necessary for network-dosage compensation may be recurrent network motifs in eukaryotic genomes and therefore may be an important design principle in gene network assembly in cells.