Comparative analysis of genome-scale, base-resolution DNA methylation profiles across 580 animal species

Klughammer, Johanna; Romanovskaia, Daria; Nemc, Amelie; Posautz, Annika; Seid, Charlotte; Schuster, Linda C.; Keinath, Melissa C.; Ramos, Juan Sebastian Lugo; Kosack, Lindsay; Evankow, Ann; Printz, Dieter; Kirchberger, Stefanie; Ergüner, Bekir; Datlinger, Paul; Fortelny, Nikolaus; Schmidl, Christian; Farlik, Matthias; Skjærven, Kaja H.; Bergthaler, Andréas; Liedvogel, Miriam; Thaller, Denise; Burger, Pamela A.; Hermann, Marcela; Distel, Martin; Distel, Daniel L.; Kübber‐Heiss, Anna; Bock, Christoph

doi:10.1038/s41467-022-34828-y

Cited by 48 publications

(46 citation statements)

References 129 publications

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“…Therefore, the patterns we observe may not necessarily be representative of genome-wide patterns. RRBS remains however a powerful and cost-effective means of methylome interrogation (see also Klughammer et al 2023 ). Secondly, the retention of individual-specific CpG sites can lead to the detection of DM simply due to differences in the abundance of CpGs available to be methylated—that is, directly due to SNPs ( Wulfridge et al 2019 ).…”

Section: Discussionmentioning

confidence: 99%

High Nucleotide Diversity Accompanies Differential DNA Methylation in Naturally Diverging Populations

Ord

Gossmann²,

Adrian‐Kalchhauser

2023

Molecular Biology and Evolution

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Epigenetic mechanisms such as DNA methylation (DNAme) are thought to comprise an invaluable adaptive toolkit in the early stages of local adaptation, especially when genetic diversity is constrained. However, the link between genetic diversity and DNAme has been scarcely examined in natural populations, despite its potential to shed light on the evolutionary forces acting on methylation state. Here, we analysed reduced-representation bisulfite sequencing and whole genome pool-seq data from marine and freshwater stickleback populations to examine the relationship between DNAme variation (between- and within-population), and nucleotide diversity in the context of freshwater adaptation. We find that sites that are differentially methylated between populations have higher underlying standing genetic variation, with diversity higher among sites that gained methylation in freshwater than those that lost it. Strikingly, while nucleotide diversity is generally lower in the freshwater population as expected from a population bottleneck, this is not the case for sites which lost methylation which instead have elevated nucleotide diversity in freshwater compared to marine. Subsequently, we show that nucleotide diversity is higher among sites with ancestrally variable methylation and also positively correlates with the sensitivity to environmentally induced methylation change. The results suggest that as selection on the control of methylation state becomes relaxed, so too does selection against mutations at the sites themselves. Increased epigenetic variance in a population is therefore likely to precede genetic diversification.

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Section: Discussionmentioning

confidence: 99%

High Nucleotide Diversity Accompanies Differential DNA Methylation in Naturally Diverging Populations

Ord

Gossmann²,

Adrian‐Kalchhauser

2023

Molecular Biology and Evolution

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“…genomic inversions or duplications. Furthermore, the high GpC content in all de novo transcripts could be associated with low methylation, even though genomes methylation is less observed in invertebrate genomes than vertebrates (Klughammer et al, 2023). Also, we found surprisingly low amounts of core promoter motifs upstream de novo transcripts.…”

Section: Discussionmentioning

confidence: 99%

DNA Transposons favour denovotranscript emergence through enrichment of transcription factor binding motifs

Lebherz,

Fouks,

Schmidt

et al. 2023

Preprint

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De novogenes emerge from non-coding regions of genomes via succession of mutations. Among others, such mutations activate transcription and create a new open reading frame (ORF). Although the mechanisms underlying ORFs emergence are well documented, relatively little is known about the mechanisms enabling new transcription events. Yet, in many species a continuum between absent and very prominent transcription has been reported for essentially all regions of the genome.In this study we searched forde novotranscripts by using newly assembled genomes and transcriptomes of seven inbred lines ofDrosophila melanogaster, originating from six European and one African population. This setup allowed us to detect line specificde novotranscripts, and compare them to their homologous non-transcribed regions in other lines, as well as genic and intergenic control sequences. We studied the association with transposable elements and the enrichment of transcription factor motifs upstream ofde novoemerged transcripts and compared them with regulatory elements.We found thatde novotranscripts overlap with TEs more often than expected by chance. The emergence of new transcripts correlates with high CpG islands and regions of TEs activity. Moreover, upstream regions ofde novotranscripts are highly enriched with regulatory motifs. Such motifs abound in new transcripts overlapping with TEs, particularly DNA TEs, and are more conserved upstreamde novotranscripts than upstream their non-transcribed homologs. Overall, our study demonstrates that TEs insertion is important for transcript emergence, partly by introducing new regulatory motifs from DNA TE families.

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“…For example, Fan et al (2014) reported that Tibetan macaques possess more nonsynonymous variants in genes related to immune response and glucose metabolism than rhesus and crab-eating macaques. Studies have demonstrated that DNA methylation levels differ among species (Klughammer et al, 2023). However, no studies have focused on the DNA methylation levels between different macaques and their correlation with gene expression levels.…”

Section: Introductionmentioning

confidence: 99%

DNA methylation and transcriptome analysis reveal epigenomic differences among three macaque species

Wang,

Liu,

Lan

et al. 2023

Evolutionary Applications

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Macaques (genus Macaca) are the most widely distributed non‐human primates, and their evolutionary history, gene expression profiles, and genetic differences have been extensively studied. However, the DNA methylomes of macaque species are not available in public databases, which hampers understanding of epigenetic differences among macaque species. Epigenetic modifications can potentially affect development, physiology, behavior, and evolution. Here, we investigated the methylation patterns of the Tibetan macaque (M. thibetana; TM), Chinese rhesus macaque (M. mulatta lasiota; CR), and crab‐eating macaque (M. fascicularis; CE) through whole‐genome bisulfite sequencing from peripheral blood. We compared genome‐wide methylation site information for the three species. We identified 12,128 (CR vs. CE), 59,165 (CR vs. TM), and 39,751 (CE vs. TM) differentially methylated regions (DMRs) in the three macaques. Furthermore, we obtained the differentially expressed genes (DEGs) among the three macaque species. The differences between CR and CE were smaller at both the methylome and transcriptome levels than compared with TM (CR vs. TM and CE vs. TM). We also found a change in the density of single nucleotide mutations in DMRs relative to their flanking regions, indicating a potential mechanism through which genomic alterations may modulate methylation landscapes, thereby influencing the transcriptome. Functional enrichment analyses showed the DMR‐related genes were enriched in developmental processes and neurological functions, such as the growth hormone‐related pathway, insulin secretion pathway, thyroid hormone synthesis pathway, morphine addiction, and GABAergic synapses. These differences may be associated with variations in physiology and habitat among the macaques. Our study provides one of the first genome‐wide comparisons of genetic, gene expression, and epigenetic variations across different macaques. Our results should facilitate further research on comparative genomic and genetic differences in macaque species.

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Comparative analysis of genome-scale, base-resolution DNA methylation profiles across 580 animal species

Cited by 48 publications

References 129 publications

High Nucleotide Diversity Accompanies Differential DNA Methylation in Naturally Diverging Populations

High Nucleotide Diversity Accompanies Differential DNA Methylation in Naturally Diverging Populations

DNA Transposons favour denovotranscript emergence through enrichment of transcription factor binding motifs

DNA methylation and transcriptome analysis reveal epigenomic differences among three macaque species

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