Genomic analysis reveals major determinants ofcis-regulatory variation inCapsella 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.allele-specific expression | fitness effects | purifying selection | positive selection | gene body methylation U nderstanding the causes of regulatory variation is of major importance for many areas of biology and medicine (1). Much interest has centered on cis-regulatory variation, which has long been thought to be particularly important for adaptation (2-5). Like other quantitative traits, cis-regulatory variation is expected to be shaped by the interplay of mutation, selection, and drift. However, the relative importance of these forces remains unclear in most species.Recently, prospects for quantifying cis-regulatory variation have greatly improved, and, as a result, ample heritable cis-regulatory variation has been identified in many species (6); this is resulting in a growing consensus that a large amount of standing cis-regulatory variation is under weak purifying selection (7-9). Clarifying why the impact of purifying selection varies across the genome is therefore important to understand the maintenance of cis-regulatory variation.Variation in the intensity of purifying selection across the genome can result from differences in selective constraint that are due to the specific functions of...

RPASE: Individual‐based allele‐specific expression detection without prior knowledge of haplotype phase

“…Previous studies found that genes with ASE might be under relaxed purifying selection compared with genes without ASE (Josephs, Wright, Stinchcombe, & Schoen, 2017;Steige et al, 2017).…”

“…Many studies employing existing methods for ASE detection filter out read counts from closely spaced SNPs (Emerson et al, 2010;Steige et al, 2017). However, this reduces the amount of data available for study and limits the statistical power when testing for ASE.…”

“…One way to study the variability of expression for a gene is to examine the variation in gene expression as measured in the same tissue among multiple individuals (Steige, Laenen, Reimeg ard, Scofield, & Slotte, 2017). To study the relationship between expression variability and ASE, for each gene and tissue, we calculated the coefficient of variation in total expression level across individuals within a tissue where total expression level is defined as the sum of stratum counts (Equation 3) from two alleles, that is,…”

Investigating population‐scale allelic differential expression in wild populations of Oithona similis (Cyclopoida, Claus, 1866)

“…In a second study, the team was able to detect loci under ADE and selection at the same time in different human populations (Tian et al 2018). Also, approaches in a plant model, Capsella grandiflora, a species characterized by weak population structure and large effective population size, emphasized the relative impact of purifying selection and positive selection on cis-regulatory variation in populations (Josephs, Lee, Stinchcombe, & Wright, 2015;Steige, Laenen, Reimegård, Scofield, & Slotte, 2017). Our study, by focusing on whole populations of numerous individuals, offers further clues to understand the link between gene expression variation and selection.…”

Agrobacterium-mediated floral-dip transformation of the obligate outcrosser Capsella grandiflora

“…Thus, these sister species have become important models for understanding the morphological and genomic consequences of the progression from SI to selfing. The loss of SI is associated with differences in floral morphology [18], reproductive imprinting [19], and cis-gene regulation [20,21]. To date, these differences have been examined at the genomic level but not at the functional and genetic levels because C. grandiflora has, to our knowledge, not previously been the subject of studies that require its transformation.…”