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Population genomic analyses of regulatory variation and selection in Brassicaceae species
Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.ORCID iD: 0000-0002-3221-8835
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 [en]
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
Research subject
Ecology and Evolution
Identifiers
URN: urn:nbn:se:su:diva-179151ISBN: 978-91-7911-076-5 (print)ISBN: 978-91-7911-077-2 (electronic)OAI: oai:DiVA.org:su-179151DiVA, id: diva2:1413921
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: 2020-05-25Bibliographically approved
List of papers
1. Selection on accessible chromatin regions in Capsella grandiflora
Open this publication in new window or tab >>Selection on accessible chromatin regions in Capsella grandiflora
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(English)Manuscript (preprint) (Other academic)
Keywords
ATAC-sequencing, open chromatin region, gene expression variation, natural selection, functional non-coding sequences, Capsella grandiflora
National Category
Biological Sciences
Research subject
Ecology and Evolution
Identifiers
urn:nbn:se:su:diva-179147 (URN)
Available from: 2020-03-10 Created: 2020-03-10 Last updated: 2020-03-23Bibliographically approved
2. The Role of Small RNA-Based Epigenetic Silencing for Purifying Selection on Transposable Elements in Capsella grandiflora
Open this publication in new window or tab >>The Role of Small RNA-Based Epigenetic Silencing for Purifying Selection on Transposable Elements in Capsella grandiflora
2017 (English)In: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 9, no 10, p. 2911-2920Article in journal (Refereed) Published
Abstract [en]

To avoid negative effects of transposable element (TE) proliferation, plants epigenetically silence TEs using a number of mechanisms, including RNA-directed DNA methylation. These epigenetic modifications can extend outside the boundaries of TE insertions and lead to silencing of nearby genes, resulting in a trade-off between TE silencing and interference with nearby gene regulation. Therefore, purifying selection is expected to remove silenced TE insertions near genes more efficiently and prevent their accumulation within a population. To explore how effects of TE silencing on gene regulation shapes purifying selection on TEs, we analyzed whole genome sequencing data from 166 individuals of a large population of the outcrossing species Capsella grandiflora. We found that most TEs are rare, and in chromosome arms, silenced TEs are exposed to stronger purifying selection than those that are not silenced by 24-nucleotide small RNAs, especially with increasing proximity to genes. An age-of-allele test of neutrality on a subset of TEs supports our inference of purifying selection on silenced TEs, suggesting that our results are robust to varying transposition rates. Our results provide new insights into the processes affecting the accumulation of TEs in an outcrossing species and support the view that epigenetic silencing of TEs results in a trade-off between preventing TE proliferation and interference with nearby gene regulation. We also suggest that in the centromeric and pericentromeric regions, the negative aspects of epigenetic TE silencing are missing.

Keywords
transposable elements, methylation, purifying selection, gene expression, epigenetic silencing, Capsella
National Category
Biological Sciences
Research subject
Ecology and Evolution
Identifiers
urn:nbn:se:su:diva-151594 (URN)10.1093/gbe/evx206 (DOI)
Available from: 2018-01-16 Created: 2018-01-16 Last updated: 2020-03-23Bibliographically approved
3. Single-cell expression noise and gene-body methylation in Arabidopsis thaliana
Open this publication in new window or tab >>Single-cell expression noise and gene-body methylation in Arabidopsis thaliana
2019 (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.

National Category
Biological Sciences
Research subject
Ecology and Evolution
Identifiers
urn:nbn:se:su:diva-171987 (URN)10.1038/s41437-018-0181-z (DOI)000474747800001 ()30651589 (PubMedID)
Available from: 2019-08-30 Created: 2019-08-30 Last updated: 2020-03-23Bibliographically approved
4. Impact of demography on linked selection in two outcrossing Brassicaceae species
Open this publication in new window or tab >>Impact of demography on linked selection in two outcrossing Brassicaceae species
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2019 (English)In: Ecology and Evolution, ISSN 2045-7758, E-ISSN 2045-7758, Vol. 9, no 17, p. 9532-9545Article in journal (Refereed) Published
Abstract [en]

Genetic diversity is shaped by mutation, genetic drift, gene flow, recombination, and selection. The dynamics and interactions of these forces shape genetic diversity across different parts of the genome, between populations and species. Here, we have studied the effects of linked selection on nucleotide diversity in outcrossing populations of two Brassicaceae species, Arabidopsis lyrata and Capsella grandiflora, with contrasting demographic history. In agreement with previous estimates, we found evidence for a modest population size expansion thousands of generations ago, as well as efficient purifying selection in C. grandiflora. In contrast, the A. lyrata population exhibited evidence for very recent strong population size decline and weaker efficacy of purifying selection. Using multiple regression analyses with recombination rate and other genomic covariates as explanatory variables, we can explain 47% of the variance in neutral diversity in the C. grandiflora population, while in the A. lyrata population, only 11% of the variance was explained by the model. Recombination rate had a significant positive effect on neutral diversity in both species, suggesting that selection at linked sites has an effect on patterns of neutral variation. In line with this finding, we also found reduced neutral diversity in the vicinity of genes in the C. grandiflora population. However, in A. lyrata no such reduction in diversity was evident, a finding that is consistent with expectations of the impact of a recent bottleneck on patterns of neutral diversity near genes. This study thus empirically demonstrates how differences in demographic history modulate the impact of selection at linked sites in natural populations.

Keywords
demography, distribution of fitness effects, linked selection, neutral genetic diversity, purifying selection, recombination
National Category
Biological Sciences
Research subject
Ecology and Evolution
Identifiers
urn:nbn:se:su:diva-173157 (URN)10.1002/ece3.5463 (DOI)000481053400001 ()
Available from: 2019-09-24 Created: 2019-09-24 Last updated: 2020-03-23Bibliographically approved

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