title: Genomic analysis reveals major determinants of cis-regulatory variation in Capsella grandiflora.
abstract: 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 (i) are under weaker purifying selection and (ii) 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 transposable elements (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 evidence for a link between gbM and cis-regulatory constraint, possibly reflecting greater dosage sensitivity of body-methylated genes. Given the extensive conservation of gbM in flowering plants, this suggests that gbM could be an important predictor of cis-regulatory variation in a wide range of plant species.
authors.affiliation: Department of Ecology and Genetics, Evolutionary Biology Centre, Uppsala University, 75236 Uppsala, Sweden.|Science for Life Laboratory, Department of Ecology, Environment, and Plant Sciences, Stockholm University, 10691 Stockholm, Sweden.
authors.forename: Kim A
authors.initials: KA
authors.lastname: Steige
authors.affiliation: Science for Life Laboratory, Department of Ecology, Environment, and Plant Sciences, Stockholm University, 10691 Stockholm, Sweden; Tanja.Slotte@su.se benjamin.laenen@su.se.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Laenen
authors.affiliation: Science for Life Laboratory, Department of Cell and Molecular Biology, Uppsala University, 75124 Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Reimegård
authors.affiliation: Department of Ecology and Genetics, Evolutionary Biology Centre, Uppsala University, 75236 Uppsala, Sweden.|Uppsala Multidisciplinary Center for Advanced Computational Science, Department of Information Technology, Uppsala University, Uppsala 75105, Sweden.
authors.forename: Douglas G
authors.identifier: 0000-0001-5235-6461
authors.initials: DG
authors.lastname: Scofield
authors.affiliation: Department of Ecology and Genetics, Evolutionary Biology Centre, Uppsala University, 75236 Uppsala, Sweden; Tanja.Slotte@su.se benjamin.laenen@su.se.|Science for Life Laboratory, Department of Ecology, Environment, and Plant Sciences, Stockholm University, 10691 Stockholm, Sweden.
authors.forename: Tanja
authors.initials: T
authors.lastname: Slotte
mesh_terms: D029687:Capsella / Q000235:genetics*; D019175:DNA Methylation; D004251:DNA Transposable Elements; D018744:DNA, Plant / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D018506:Gene Expression Regulation, Plant / Q000235:genetics*; D020868:Gene Silencing; D017343:Genes, Plant; D014644:Genetic Variation; D018745:Genome, Plant; D006115:Greece; D056186:Metagenomics / Q000379:methods; D018749:RNA, Plant / Q000235:genetics; D012641:Selection, Genetic
chemical_list: D004251:DNA Transposable Elements; D018744:DNA, Plant; D018749:RNA, Plant
keywords: allele-specific expression; fitness effects; gene body methylation; positive selection; purifying selection