Population-scale long-read sequencing uncovers transposable elements contributing to gene expression variation and associated with adaptive signatures in Drosophila melanogaster

High quality reference genomes are crucial to understanding genome function, structure and evolution. The availability of reference genomes has allowed us to start inferring the role of genetic variation in biology, disease, and biodiversity conservation. However, analyses across organisms demonstrate that a single reference genome is not enough to capture the global genetic diversity present in populations. In this work, we generated 32 high-quality reference genomes for the well-known model species D. melanogaster and focused on the identification and analysis of transposable element variation as they are the most common type of structural variant. We showed that integrating the genetic variation across natural populations from five climatic regions increases the number of detected insertions by 58%. Moreover, 26% to 57% of the insertions identified using long-reads were missed by short-reads methods. We also identified hundreds of transposable elements associated with gene expression variation and new TE variants likely to contribute to adaptive evolution in this species. Our results highlight the importance of incorporating the genetic variation present in natural populations to genomic studies, which is essential if we are to understand how genomes function and evolve.

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Gene expression variation in natural populations of hexaploid and allododecaploid Spartina species (Poaceae)

Plant Systematics and Evolution ◽

10.1007/s00606-017-1446-3 ◽

2017 ◽

Vol 303 (8) ◽

pp. 1061-1079 ◽

Cited By ~ 10

Author(s):

Julie Ferreira de Carvalho ◽

Julien Boutte ◽

Pierre Bourdaud ◽

Houda Chelaifa ◽

Kader Ainouche ◽

...

Keyword(s):

Gene Expression ◽

Natural Populations ◽

Gene Expression Variation ◽

Expression Variation ◽

Spartina Species

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The roles of plasticity and evolutionary change in shaping gene expression variation in natural populations of extremophile fish

Molecular Ecology ◽

10.1111/mec.14360 ◽

2017 ◽

Vol 26 (22) ◽

pp. 6384-6399 ◽

Cited By ~ 15

Author(s):

Courtney N. Passow ◽

Chathurika Henpita ◽

Jennifer H. Shaw ◽

Corey R. Quackenbush ◽

Wesley C. Warren ◽

...

Keyword(s):

Gene Expression ◽

Natural Populations ◽

Evolutionary Change ◽

Gene Expression Variation ◽

Expression Variation

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Transposable elements are important contributors to standing variation in gene expression in Capsella grandiflora

10.1101/289173 ◽

2018 ◽

Author(s):

Jasmina Uzunović ◽

Emily B. Josephs ◽

John R. Stinchcombe ◽

Stephen I. Wright

Keyword(s):

Gene Expression ◽

Single Nucleotide Polymorphisms ◽

Transposable Elements ◽

Genomic Diversity ◽

Nucleotide Polymorphisms ◽

Mobile Dna ◽

Gene Expression Variation ◽

Single Nucleotide ◽

Expression Variation ◽

A Genome

AbstractTransposable elements (TEs) make up a significant portion of eukaryotic genomes, and thus are important drivers of genome evolution. However, the evolutionary forces controlling TE copy number and the extent to which TEs affect phenotypic variation on a genome-wide scale are still unclear. We characterised TE insertion polymorphism and its effects on gene expression in 124 whole genome sequences from a single population of Capsella grandiflora. The frequency of insertions was negatively correlated with distance to genes, as well as density of conserved non-coding elements, suggesting that the negative effects of TEs on gene regulation are important in limiting their abundance. Rare TE variants strongly influence gene expression variation, predominantly through downregulation. In contrast, rare single nucleotide polymorphisms (SNPs) contribute equally to up- and down-regulation, but have a weaker effect. Taken together, these results imply that TEs are a significant contributor to gene expression variation and can be more likely than rare SNPs to cause extreme changes in gene expression.Author SummaryTransposable elements (TEs), mobile DNA elements with the ability to excise from the genome and reinsert in new locations, are important components of genomic diversity. Due to their abundance and mobility, TEs play an influential role in genomic evolution, often deleterious. Here we show that TEs in a population of the plant Capsella grandiflora are most deleterious when they insert in genic and regulatory regions. We find that TEs indeed are associated with unusual levels of gene expression, predominantly decreased expression.Furthermore, this effect is stronger than the association of single nucleotide polymorphisms with gene expression variation, highlighting the importance of TE contribution to the maintenance of expression variation.

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Transposable Elements Are Important Contributors to Standing Variation in Gene Expression in Capsella Grandiflora

Molecular Biology and Evolution ◽

10.1093/molbev/msz098 ◽

2019 ◽

Vol 36 (8) ◽

pp. 1734-1745 ◽

Cited By ~ 8

Author(s):

Jasmina Uzunović ◽

Emily B Josephs ◽

John R Stinchcombe ◽

Stephen I Wright

Keyword(s):

Gene Expression ◽

Transposable Elements ◽

Eqtl Analysis ◽

Nucleotide Polymorphisms ◽

Gene Expression Variation ◽

Negative Effects ◽

Rare Snps ◽

Expression Variation ◽

Standing Variation ◽

A Genome

Abstract Transposable elements (TEs) make up a significant portion of eukaryotic genomes and are important drivers of genome evolution. However, the extent to which TEs affect gene expression variation on a genome-wide scale in comparison with other types of variants is still unclear. We characterized TE insertion polymorphisms and their association with gene expression in 124 whole-genome sequences from a single population of Capsella grandiflora, and contrasted this with the effects of single nucleotide polymorphisms (SNPs). Population frequency of insertions was negatively correlated with distance to genes, as well as density of conserved noncoding elements, suggesting that the negative effects of TEs on gene regulation are important in limiting their abundance. Rare TE variants strongly influence gene expression variation, predominantly through downregulation. In contrast, rare SNPs contribute equally to up- and down-regulation, but have a weaker individual effect than TEs. An expression quantitative trait loci (eQTL) analysis shows that a greater proportion of common TEs are eQTLs as opposed to common SNPs, and a third of the genes with TE eQTLs do not have SNP eQTLs. In contrast with rare TE insertions, common insertions are more likely to increase expression, consistent with recent models of cis-regulatory evolution favoring enhancer alleles. Taken together, these results imply that TEs are a significant contributor to gene expression variation and are individually more likely than rare SNPs to cause extreme changes in gene expression.

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Transposable elements contribute to genome dynamics and gene expression variation in the fungal plant pathogen Verticillium dahliae

10.1101/2021.01.25.428111 ◽

2021 ◽

Author(s):

David E Torres ◽

Bart PHJ Thomma ◽

Michael F Seidl

Keyword(s):

Gene Expression ◽

Transposable Elements ◽

Verticillium Dahliae ◽

Plant Pathogen ◽

Plant Pathogens ◽

Gene Expression Variation ◽

Expression Variation ◽

Regulatory Variation ◽

Fungal Plant Pathogen ◽

Genomic Regions

AbstractTransposable elements (TEs) are a major source of genetic and regulatory variation in their host genome and are consequently thought to play important roles in evolution. Many fungal and oomycete plant pathogens have evolved dynamic and TE-rich genomic regions containing genes that are implicated in host colonization. TEs embedded in these regions have typically been thought to accelerate the evolution of these genomic compartments, but little is known about their dynamics in strains that harbor them. Here, we used whole-genome sequencing data of 42 strains of the fungal plant pathogen Verticillium dahliae to systematically identify polymorphic TEs that may be implicated in genomic as well as in gene expression variation. We identified 2,523 TE polymorphisms and characterize a subset of 8% of the TEs as dynamic elements that are evolutionary younger, less methylated, and more highly expressed when compared with the remaining 92% of the TE complement. As expected, the dynamic TEs are enriched in the dynamic genomic regions. Besides, we observed an association of dynamic TEs with pathogenicity-related genes that localize nearby and that display high expression levels. Collectively, our analyses demonstrate that TE dynamics in V. dahliae contributes to genomic variation, correlates with expression of pathogenicity-related genes, and potentially impacts the evolution of dynamic genomic regions.Significance statementTransposable elements (TEs) are ubiquitous components of genomes and are major sources of genetic and regulatory variation. Many plant pathogens have evolved TE-rich genomic regions containing genes with roles in host colonization, and TEs are thought to contribute to accelerated evolution of these dynamic regions. We analyzed the fungal plant pathogen Verticillium dahliae to identify TE variation between strains and to demonstrate that polymorphic TEs have specific characteristic that separates them from the majority of TEs. Polymorphic TEs are enriched in dynamic genomic regions and are associated with structural variants and highly expressed pathogenicity-related genes. Collectively, our results provide evidence for the hypothesis that dynamic TEs contribute to increased genomic diversity, functional variation, and the evolution of dynamic genomic regions.

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Faculty Opinions recommendation of Abundant contribution of short tandem repeats to gene expression variation in humans.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725994101.793513449 ◽

2016 ◽

Author(s):

Melanie Bahlo

Keyword(s):

Gene Expression ◽

Short Tandem Repeats ◽

Tandem Repeats ◽

Gene Expression Variation ◽

Expression Variation ◽

Short Tandem

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Massively parallel gene expression variation measurement of a synonymous codon library

BMC Genomics ◽

10.1186/s12864-021-07462-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Alexander Schmitz ◽

Fuzhong Zhang

Keyword(s):

Gene Expression ◽

Codon Usage ◽

Single Cells ◽

Massively Parallel ◽

Protein Abundance ◽

Translation Efficiency ◽

Gene Expression Variation ◽

Expression Variation ◽

Change In Mean ◽

Adaptation Index

Abstract Background Cell-to-cell variation in gene expression strongly affects population behavior and is key to multiple biological processes. While codon usage is known to affect ensemble gene expression, how codon usage influences variation in gene expression between single cells is not well understood. Results Here, we used a Sort-seq based massively parallel strategy to quantify gene expression variation from a green fluorescent protein (GFP) library containing synonymous codons in Escherichia coli. We found that sequences containing codons with higher tRNA Adaptation Index (TAI) scores, and higher codon adaptation index (CAI) scores, have higher GFP variance. This trend is not observed for codons with high Normalized Translation Efficiency Index (nTE) scores nor from the free energy of folding of the mRNA secondary structure. GFP noise, or squared coefficient of variance (CV2), scales with mean protein abundance for low-abundant proteins but does not change at high mean protein abundance. Conclusions Our results suggest that the main source of noise for high-abundance proteins is likely not originating at translation elongation. Additionally, the drastic change in mean protein abundance with small changes in protein noise seen from our library implies that codon optimization can be performed without concerning gene expression noise for biotechnology applications.

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