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Single-cell expression noise and gene-body methylation in Arabidopsis thaliana
Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Stockholm University, Science for Life Laboratory (SciLifeLab).ORCID iD: 0000-0002-3221-8835
Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Stockholm University, Science for Life Laboratory (SciLifeLab).
Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Stockholm University, Science for Life Laboratory (SciLifeLab).ORCID iD: 0000-0001-6020-5102
Number of Authors: 42019 (English)In: Heredity, ISSN 0018-067X, E-ISSN 1365-2540, Vol. 123, no 2, p. 81-91Article in journal (Refereed) Published
Abstract [en]

Gene-body methylation (gbM) refers to an increased level of methylated cytosines specifically in a CG sequence context within genes. gbM is found in plant genes with intermediate expression level, which evolve slowly, and is often broadly conserved across millions of years of evolution. Intriguingly however, some plants lack gbM, and thus it remains unclear whether gbM has a function. In animals, there is support for a role of gbM in reducing erroneous transcription and transcription noise, but so far most studies in plants have tested for an effect of gbM on expression level, not noise. Here, we therefore tested whether gbM was associated with reduced expression noise in Arabidopsis thaliana, using single-cell transcriptome sequencing data from root quiescent centre cells. We find that gbM genes have lower expression noise levels than unmethylated genes. However, an analysis of covariance revealed that, if other genomic features are taken into account, this association disappears. Nonetheless, gbM genes were more consistently expressed across single-cell samples, supporting previous inference that gbM genes are constitutively expressed. Finally, we observed that fewer RNAseq reads map to introns of gbM genes than to introns of unmethylated genes, which indicates that gbM might be involved in reducing erroneous transcription by reducing intron retention.

Place, publisher, year, edition, pages
2019. Vol. 123, no 2, p. 81-91
National Category
Biological Sciences
Research subject
Ecology and Evolution
Identifiers
URN: urn:nbn:se:su:diva-171987DOI: 10.1038/s41437-018-0181-zISI: 000474747800001PubMedID: 30651589OAI: oai:DiVA.org:su-171987DiVA, id: diva2:1347256
Available from: 2019-08-30 Created: 2019-08-30 Last updated: 2022-03-23Bibliographically approved
In thesis
1. Population genomic analyses of regulatory variation and selection in Brassicaceae species
Open this publication in new window or tab >>Population genomic analyses of regulatory variation and selection in Brassicaceae species
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The impact of selection on regulatory variation and the contribution of regulatory changes to phenotypic variation has long been debated in evolutionary genetics. Because cis-regulatory elements such as promoters and enhancers can be difficult to identify, it has been more challenging to quantify the impact of selection on variation in cis-regulatory regions than in protein-coding regions. In this thesis, I use genomic tools to investigate gene expression variation and selection in Brassicaceae species. First, I investigated the genomic impact of selection on putative cis-regulatory regions in the genome of the crucifer species Capsella grandiflora (Brassicaceae) (Paper I). I used an assay for transposase-accessible chromatin with high throughput sequencing (ATAC-seq) to empirically identify putative cis-regulatory regions as those located in accessible chromatin regions (ACRs) in the genome of the crucifer species Capsella grandiflora. Based on whole-genome resequencing data from a natural population, I then showed that ACRs are under stronger purifying selection than other intergenic regions and that they are depleted for transposable element (TE) insertions and enriched for expression quantitative trait loci (eQTL), as would be expected if ACRs are enriched for functional elements affecting gene expression. Second, I explored how the location and silencing of transposable elements (TEs) affects selection against TEs (Paper II). Specifically, I tested a trade-off model on epigenetic TE silencing, according to which the positive effects of TE silencing on preventing TE movement conflict with negative effects of TE silencing on nearby gene expression. I found that TE silencing through the RNA-directed DNA methylation (RdDM) pathway affects selection against TEs close to genes in C. grandiflora, which is consistent with the trade-off model. Third, I used Arabidopsis thaliana single-cell expression data to investigate the relationship between gene body methylation (gbM) and transcriptional regulation (Paper III). I found that there was an indirect correlation between gbM and gene expression noise as well as a direct correlation between gbM and gene expression consistency and potentially intron retention in Arabidopsis thaliana. Fourth, I investigated the impact of demographic history on genomic signatures of selection at linked sites (linked selection) (Paper IV). This study revealed that neutral genetic diversity in C. grandiflora with a stable effective population size is influenced by linked selection whereas in Arabidopsis lyrata, which underwent a recent and strong bottleneck, neutral diversity is mainly affected by population size change. In summary, this thesis offers new insights into determinants of gene expression variation, selection on genomic features linked to gene expression alteration, as well as on the effect of demographic history on linked selection patterns in Brassicaceae.

Place, publisher, year, edition, pages
Stockholm: Department of Ecology, Environment and Plant Sciences, 2020. p. 48
Keywords
Capsella grandiflora, Arabidopsis thaliana, Arabidopsis lyrata, natural selection, gene expression variation, DNA and gene body methylation, transposable elements, DNA accessibility, gene expression noise, epigenetic silencing, linked selection
National Category
Genetics and Genomics
Research subject
Ecology and Evolution
Identifiers
urn:nbn:se:su:diva-179151 (URN)978-91-7911-076-5 (ISBN)978-91-7911-077-2 (ISBN)
Public defence
2020-05-08, Vivi Täckholmsalen (Q-salen), NPQ-huset, Svante Arrhenius väg 20, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 1: Manuscript.

Available from: 2020-04-15 Created: 2020-03-11 Last updated: 2025-02-07Bibliographically approved

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Horvath, RobertLaenen, BenjaminSlotte, Tanja

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