Selection on Accessible Chromatin Regions inCapsella grandiflora

Abstract

Accurate estimates of genome-wide rates and fitness effects of new mutations are essential for an improved understanding of molecular evolutionary processes. Although eukaryotic genomes generally contain a large non-coding fraction, functional non-coding regions and fitness effects of mutations in such regions are still incompletely characterized. A promising approach to characterize functional non-coding regions relies on identifying accessible chromatin regions (ACRs) tightly associated with regulatory DNA. Here, we applied this approach to identify and estimate selection on ACRs in Capsella grandiflora, a crucifer species ideal for population genomic quantification of selection due to its favourable population demography. We describe a population-wide ACR distribution based on ATAC-seq data for leaf samples of 16 individuals from a natural population. We use population genomic methods to estimate fitness effects and proportions of positively selected fixations (α) in ACRs and find that intergenic ACRs harbor a considerable fraction of weakly deleterious new mutations, as well as a significantly higher proportion of strongly deleterious mutations than comparable inaccessible intergenic regions. ACRs are enriched for expression quantitative trait loci (eQTL) and depleted of transposable element (TE) insertions, as expected if intergenic ACRs are under selection because they harbor regulatory regions. By integrating empirical identification of intergenic ACRs with analyses of eQTL and population genomic analyses of selection, we demonstrate that intergenic regulatory regions are an important source of nearly neutral mutations. These results improve our understanding of selection on non-coding regions and the role of nearly neutral mutations for evolutionary processes in outcrossing Brassicaceae species.

Globally Relaxed Selection and Local Adaptation inBoechera stricta

“…Therefore, natural selection is expected to be prevalent in species with large N e , and relaxed in species with small N e . Consistent with this expectation, high levels of adaptive divergence have been detected in species with large N e , for example, Drosophila ( Bierne and Eyre-Walker 2004 ), rodents ( Halligan et al 2010 ), poplar ( Lin et al 2018 ), oaks ( Liang et al 2021 ), and the outcrossing crucifer Capsella grandiflora ( Slotte et al 2010 ; Williamson et al 2014 ; Josephs et al 2017 ; Horvath et al 2021 ), whereas low levels of adaptive divergence are found in hominids ( Eyre-Walker and Keightley 2009 ) and Arabidopsis thaliana ( Foxe et al 2008 ; Hämälä and Tiffin 2020 ), which have small N e . A positive correlation between the rates of adaptive evolution and N e was also observed in plants and animals, suggesting significant effects of N e in determining the level of adaptive divergence ( Strasburg et al 2011 ; Galtier 2016 ; Nam et al 2017 ).…”

“…Evidence that rare variants have a great impact on gene expression suggests that pervasive purifying selection has acted on cis -acting regulatory variants in humans ( Hernandez et al 2019 ). The strength of positive and negative selection varies among species ( Gossmann et al 2010 ; Grivet et al 2017 ; Lin et al 2018 ; Zhao et al 2020 ), and also varies across different portions of the genome ( Williamson et al 2014 ; Josephs et al 2017 ; Uricchio et al 2019 ; Horvath et al 2021 ).…”

“…However, studies have detected strong signals of selection in conserved non-coding sequences (CNSs) ( Andolfatto 2005 ; Kousathanas et al 2011 ; Haudry et al 2013 ; Williamson et al 2014 ). To date, the CNSs were only characterized in a few species, for example, Drosophila ( Andolfatto 2005 ), human ( Davydov et al 2010 ; Lindblad-Toh et al 2011 ), rodents ( Kousathanas et al 2011 ), and Brassicaceae species ( Haudry et al 2013 ; Williamson et al 2014 ; Horvath et al 2021 ). We know little about the strength and extent of selection on CNS, as well as the relative importance of selection acting in CNS versus coding regions.…”

Environmental response in gene expression and DNA methylation reveals factors influencing the adaptive potential ofArabidopsis lyrata

“…Although studies of environmentally responsive genes have discovered a wide range of expression responses (Hodgins-Davis and Townsend, 2009), many populations and species have reacted consistently to environmental stress (He et al, 2021; Lowry et al, 2013; Wos et al, 2021a; Yeaman et al, 2014). As gene expression is primarily controlled by regulatory elements acting either in cis (affecting nearby genes) or trans (affecting distant genes), the conserved expression responses are indicative of conserved regulatory systems (Horvath et al, 2021; Lu et al, 2019; Rodgers-Melnick et al, 2016). Such consistently expressed genes have also shown signals of strong purifying selection at the coding regions (Hodgins et al, 2016; Hunt et al, 2013; Lasky et al, 2014; Lowry et al, 2013; Zhang et al, 2017), suggesting that the regulatory conservation is frequently coupled with the conservation of the gene product.…”

“…Although studies of environmentally responsive genes have discovered a wide range of expression responses (Hodgins-Davis and Townsend, 2009), many populations and species have reacted consistently to environmental stress (He et al, 2021;Lowry et al, 2013;Wos et al, 2021a;Yeaman et al, 2014). As gene expression is primarily controlled by regulatory elements acting either in cis (affecting nearby genes) or trans (affecting distant genes), the conserved expression responses are indicative of conserved regulatory systems (Horvath et al, 2021;Lu et al, 2019;Rodgers-Melnick et al, 2016).…”