PT  - JOURNAL ARTICLE
AU  - Bryan Sands
AU  - Soo Yun
AU  - Alexander R. Mendenhall
TI  - Introns Control Intrinsic Noise
AID  - 10.1101/746263
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 746263
4099  - http://biorxiv.org/content/early/2019/09/04/746263.short
4100  - http://biorxiv.org/content/early/2019/09/04/746263.full
AB  - Understanding sources of variation in gene expression is important because they underlie variation in traits. Studies in microbes and cell culture have revealed significant, intrinsic nongenetic, nonenvironmental axes of variation in gene expression. Stochastic autosomal allele bias (including monoallelic expression), which can be quantified as intrinsic noise, is one of these natural axes. Higher intrinsic noise means a higher chance of observing a cell with allelically biased expression. Here, we surveyed intrinsic noise in the tissues of C. elegans using fluorescent reporter alleles controlled by the hsp-90 promoter. We saw visually striking allele bias present in several distinct cell types, including nerves, muscles and intestines. Because intron sequences can both alter chromatin markings and increase expression level, we hypothesized that introns increase the probability of fully expressing both alleles of a gene, thereby decreasing intrinsic noise. We found that intrinsic noise decreases by an order of magnitude when alleles contain synthetic or natural introns. We found that this is true in both diploid muscle cells and polyploid intestine cells. Our results show introns control intrinsic noise for other distinctly regulated genes (vit-2 and hsp-16.2). As in prior studies in yeast, we found these distinct promoters also impact intrinsic noise. Finally, we found that introns control intrinsic noise using a 5’-position dependent mechanism. Intron control of intrinsic noise may help explain why some genes have lost introns, why so many genes have introns, and why deep intronic mutations can result in allele silencing and disease.