Phytophthora methylomes modulated by expanded 6mA methyltransferases are associated with adaptive genome regions

AbstractFilamentous plant pathogen genomes often display a bipartite architecture with gene sparse, repeat-rich compartments serving as a cradle for adaptive evolution. However, the extent to which this “two-speed” genome architecture is associated with genome-wide epigenetic modifications is unknown. Here, we show that the oomycete plant pathogens Phytophthora infestans and Phytophthora sojae possess functional adenine N6- methylation (6mA) methyltransferases that modulate patterns of 6mA marks across the genome. In contrast, 5-methylcytosine (5mC) could not be detected in the two Phytophthora species. Methylated DNA IP Sequencing (MeDIP-seq) of each species revealed that 6mA is depleted around the transcriptional starting sites (TSS) and is associated with low expressed genes, particularly transposable elements. Remarkably, genes occupying the gene-sparse regions have higher levels of 6mA compared to the remainder of both genomes, possibly implicating the methylome in adaptive evolution of Phytophthora. Among three putative adenine methyltransferases, DAMT1 and DAMT3 displayed robust enzymatic activities. Surprisingly, single knockouts of each of the 6mA methyltransferases in P. sojae significantly reduced in vivo 6mA levels, indicating that the three enzymes are not fully redundant. MeDIP-seq of the damt3 mutant revealed uneven patterns of 6mA methylation across genes, suggesting that PsDAMT3 may have a preference for gene body methylation after the TSS. Our findings provide evidence that 6mA modification is an epigenetic mark of Phytophthora genomes and that complex patterns of 6mA methylation by the expanded 6mA methyltransferases may be associated with adaptive evolution in these important plant pathogens.

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Phylogenetic Shifts in Gene Body Methylation Correlate with Gene Expression and Reflect Trait Conservation

Molecular Biology and Evolution ◽

10.1093/molbev/msz195 ◽

2019 ◽

Vol 37 (1) ◽

pp. 31-43 ◽

Cited By ~ 3

Author(s):

Danelle K Seymour ◽

Brandon S Gaut

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Molecular Evolution ◽

Methylation Status ◽

Evolutionary Constraint ◽

Gene Body ◽

Gene Body Methylation ◽

Plant Genomes ◽

Genome Wide ◽

Rates Of Molecular Evolution

Abstract A subset of genes in plant genomes are labeled with DNA methylation specifically at CG residues. These genes, known as gene-body methylated (gbM), have a number of associated characteristics. They tend to have longer sequences, to be enriched for intermediate expression levels, and to be associated with slower rates of molecular evolution. Most importantly, gbM genes tend to maintain their level of DNA methylation between species, suggesting that this trait is under evolutionary constraint. Given the degree of conservation in gbM, we still know surprisingly little about its function in plant genomes or whether gbM is itself a target of selection. To address these questions, we surveyed DNA methylation across eight grass (Poaceae) species that span a gradient of genome sizes. We first established that genome size correlates with genome-wide DNA methylation levels, but less so for genic levels. We then leveraged genomic data to identify a set of 2,982 putative orthologs among the eight species and examined shifts of methylation status for each ortholog in a phylogenetic context. A total of 55% of orthologs exhibited a shift in gbM, but these shifts occurred predominantly on terminal branches, indicating that shifts in gbM are rarely conveyed over time. Finally, we found that the degree of conservation of gbM across species is associated with increased gene length, reduced rates of molecular evolution, and increased gene expression level, but reduced gene expression variation across species. Overall, these observations suggest a basis for evolutionary pressure to maintain gbM status over evolutionary time.

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Phylogenetic shifts in gene body methylation correlate with gene expression and reflect trait conservation

10.1101/687186 ◽

2019 ◽

Cited By ~ 1

Author(s):

Danelle K. Seymour ◽

Brandon S. Gaut

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Molecular Evolution ◽

Methylation Status ◽

Evolutionary Constraint ◽

Gene Body ◽

Gene Body Methylation ◽

Plant Genomes ◽

Genome Wide ◽

Rates Of Molecular Evolution

ABSTRACTA subset of genes in plant genomes are labeled with DNA methylation specifically at CG residues. These genes, known as gene-body methylated (gbM), have a number of associated characteristics. They tend to have longer sequences, to be enriched for intermediate expression levels, and to be associated with slower rates of molecular evolution. Most importantly, gbM genes tend to maintain their level of DNA methylation between species, suggesting that this trait is under evolutionary constraint. Given the degree of conservation in gbM, we still know surprisingly little about its function in plant genomes or whether gbM is itself a target of selection. To address these questions, we surveyed DNA methylation across eight grass (Poaceae) species that span a gradient of genome sizes. We first established that genome size correlates with genome-wide DNA methylation levels, but less so for genic levels. We then leveraged genomic data to identify a set of 2,982 putative orthologs among the eight species and examined shifts of methylation status for each ortholog in a phylogenetic context. A total of 55% of orthologs exhibited a shift in gbM, but these shifts occurred predominantly on terminal branches, indicating that shifts in gbM are rarely conveyed over time. Finally, we found that the degree of conservation of gbM across species is associated with increased gene length, reduced rates of molecular evolution, and increased gene expression level, but reduced gene expression variation across species. Overall, these observations suggest a basis for evolutionary pressure to maintain gbM status over evolutionary time.

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Role of gene body methylation in acclimatization and adaptation in a basal metazoan

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1813749115 ◽

2018 ◽

Vol 115 (52) ◽

pp. 13342-13346 ◽

Cited By ~ 28

Author(s):

Groves Dixon ◽

Yi Liao ◽

Line K. Bay ◽

Mikhail V. Matz

Keyword(s):

Housekeeping Genes ◽

Gene Body ◽

Gene Body Methylation ◽

Expression Change ◽

Transgenerational Plasticity ◽

Basal Metazoan ◽

Genome Wide ◽

Environmentally Responsive ◽

Shifting Balance ◽

Environmental Responses

Gene body methylation (GBM) has been hypothesized to modulate responses to environmental change, including transgenerational plasticity, but the evidence thus far has been lacking. Here we show that coral fragments reciprocally transplanted between two distant reefs respond predominantly by increase or decrease in genome-wide GBM disparity: The range of methylation levels between lowly and highly methylated genes becomes either wider or narrower. Remarkably, at a broad functional level this simple adjustment correlated very well with gene expression change, reflecting a shifting balance between expressions of environmentally responsive and housekeeping genes. In our experiment, corals in a lower-quality habitat up-regulated genes involved in environmental responses, while corals in a higher-quality habitat invested more in housekeeping genes. Transplanted fragments showing closer GBM match to local corals attained higher fitness characteristics, which supports GBM’s role in acclimatization. Fixed differences in GBM between populations did not align with plastic GBM changes and were mostly observed in genes with elevated FST, which suggests that they arose predominantly through genetic divergence. However, we cannot completely rule out transgenerational inheritance of acquired GBM states.

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Role of gene body methylation in coral acclimatization and adaptation

10.1101/184457 ◽

2017 ◽

Cited By ~ 1

Author(s):

Groves Dixon ◽

Yi Liao ◽

Line K. Bay ◽

Mikhail V. Matz

Keyword(s):

Gene Expression ◽

Housekeeping Genes ◽

Gene Body ◽

Transgenerational Inheritance ◽

Gene Body Methylation ◽

Transgenerational Plasticity ◽

Genome Wide ◽

Environmentally Responsive ◽

Predict Gene Expression

AbstractGene body methylation (GBM) has been hypothesized to modulate responses to environmental change, including transgenerational plasticity, but the evidence thus far has been lacking. Here we show that coral fragments reciprocally transplanted between two distant reefs respond with genome-wide increase or decrease in GBM disparity among genes. Surprisingly, this simple genome-wide adjustment predicted broad-scale gene expression changes and fragments’ fitness in the new environment. This supports GBM’s role in acclimatization, which may consist in modulating the expression balance between environmentally-responsive and housekeeping genes. At the same time, constitutive differences in GBM between populations did not align with plastic GBM changes upon transplantation and were mostly observed amongFSToutliers, indicating that they arose through genetic divergence rather than through transgenerational inheritance of acquired GBM states.One-sentence summaryGenome-wide shifts in gene body methylation predict gene expression and fitness during acclimatization but do not contribute to epigenetic divergence between populations.

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A Global Gene Body Methylation Measure Correlates Independently with Overall Survival in Solid Cancer Types

Cancers ◽

10.3390/cancers12082257 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2257

Author(s):

Dietmar Pils ◽

Elisabeth Steindl ◽

Anna Bachmayr-Heyda ◽

Sabine Dekan ◽

Stefanie Aust

Keyword(s):

Gene Expression ◽

Pancreatic Cancer ◽

Overall Survival ◽

Cancer Biology ◽

Methylation Status ◽

Cpg Methylation ◽

Gene Body ◽

Gene Body Methylation ◽

Genome Wide ◽

Cancer Types

Epigenetics, CpG methylation of CpG islands (CGI) and gene bodies (GBs), plays an important role in gene regulation and cancer biology, the former established as a transcription regulator. Genome wide CpG methylation, summarized over GBs and CGIs, was analyzed for impact on overall survival (OS) in cancer. The averaged GB and CGI methylation status of each gene was categorized into methylated and unmethylated (defined) or undefined. Differentially methylated GBs and genes associated with their GB methylation status were compared to the corresponding CGI methylation states and biologically annotated. No relevant correlations of GB and CGI methylation or GB methylation and gene expression were observed. Summarized GB methylation showed impact on OS in ovarian, breast, colorectal, and pancreatic cancer, and glioblastoma, but not in lung cancer. In ovarian, breast, and colorectal cancer more defined GBs correlated with unfavorable OS, in pancreatic cancer with favorable OS and in glioblastoma more methylated GBs correlated with unfavorable OS. The GB methylation of genes were similar over different samples and even over cancer types; nevertheless, the clustering of different cancers was possible. Gene expression differences associated with summarized GB methylation were cancer specific. A genome-wide dysregulation of gene-body methylation showed impact on the outcome in different cancers.

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