PT  - JOURNAL ARTICLE
AU  - Kim A. Steige
AU  - Benjamin Laenen
AU  - Johan Reimegård
AU  - Douglas Scofield
AU  - Tanja Slotte
TI  - Genomic analysis reveals major determinants of <em>cis</em>-regulatory variation in <em>Capsella grandiflora</em>
AID  - 10.1101/034025
DP  - 2016 Jan 01
TA  - bioRxiv
PG  - 034025
4099  - http://biorxiv.org/content/early/2016/07/29/034025.short
4100  - http://biorxiv.org/content/early/2016/07/29/034025.full
AB  - Understanding the causes of cis-regulatory variation is a long-standing aim in evolutionary biology. Although cis-regulatory variation has long been considered important for adaptation, we still have a limited understanding of the selective importance and genomic determinants of standing cis-regulatory variation. To address these questions, we studied the prevalence, genomic determinants and selective forces shaping cis-regulatory variation in the outcrossing plant Capsella grandiflora. We first identified a set of 1,010 genes with common cis-regulatory variation using analyses of allele-specific expression (ASE). Population genomic analyses of whole-genome sequences from 32 individuals showed that genes with common cis-regulatory variation are 1) under weaker purifying selection and 2) undergo less frequent positive selection than other genes. We further identified genomic determinants of cis-regulatory variation. Gene-body methylation (gbM) was a major factor constraining cis-regulatory variation, whereas presence of nearby TEs and tissue specificity of expression increased the odds of ASE. Our results suggest that most common cis-regulatory variation in C. grandiflora is under weak purifying selection, and that gene-specific functional constraints are more important for the maintenance of cis-regulatory variation than genome-scale variation in the intensity of selection. Our results agree with previous findings that suggest TE silencing affects nearby gene expression, and provide novel evidence for a link between gbM and cis-regulatory constraint, possibly reflecting greater dosage-sensitivity of body-methylated genes. Given the extensive conservation of gene-body methylation in flowering plants, this suggests that gene-body methylation could be an important predictor of cis-regulatory variation in a wide range of plant species.