Strength of stabilizing selection on the amino-acid sequence is associated with the amount of non-additive variance in gene expression.

The distinction between the additive and non-additive components of genetic trait variance has long been known to be crucial for predicting the potential of a population to respond to selection. Yet we know surprisingly little about the genomic and evolutionary factors that influence non-additive genetic variance in natural populations. Here, we use a quantitative genetic breeding design to delineate the additive and non-additive components of expression variance of 17,657 gene transcripts in the outcrossing plant Arabidopsis lyrata. We find that most of the genetic variance in gene expression is from non-additive variance. Transcripts showing the highest levels of non-additive variance tend to be longer, clustered in larger groups of co-expressed genes, and enriched in functions related to cellular differentiation or to the epigenetic reprogramming of gene expression. Furthermore, we find that genes with the most non-additive variation not only display a markedly lower rate of synonymous variation, they are also exposed to stronger stabilizing selective forces than genes with high additive variance. To the best of our knowledge, this study is the first to show that stabilizing selection on amino-acid sequences is associated with a decrease in a population's potential for adaptation of gene expression levels. ### Competing Interest Statement The authors have declared no competing interest.