Effects of Zygosity on Stochastic Gene Expression of Diploid Cells

Stochastic gene expression has been extensively studied in natural and synthetic gene expression systems. However, the majority of those contributions, if not all, were concentrated on the haploid systems, where a single allele is inherited by asexual reproduction. Largely left unexplored is the question of how much the allelic imbalance in chromatin accessibility or divergence in transcription factor binding sites would impact the organismal fitness and thus shaped the sequence evolution. Here, we explicitly consider diploid systems with homo- and heterozygous combination of alleles in the regulatory sequences rather than the primary coding sequence and characterize the genetic noise profiles associated with the zygosity. In particular, we show that the heterozygosity may arise as an outcome of evolutionary selection, when the regulatory proteins are subject to stochastic fluctuations, acting as a source of extrinsic noise. Based on this buffering mechanism in heterozygote, we discuss the relevance of our results to the recent reports on the balancing selection enriched in the cis-regulatory sequences of immune cells and epithelial cells.