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Abstract Gene duplication is a source of evolutionary novelty. DNA methylation may play a role in the evolution of duplicate genes (paralogs) through its association with gene expression. While this relationship has been examined to varying extents in a few individual species, the generalizability of these results at either a broad phylogenetic scale with species of differing duplication histories or across a population remains unknown. We applied a comparative epigenomic approach to 43 angiosperm species across the phylogeny and a population of 928 Arabidopsis (Arabidopsis thaliana) accessions, examining the association of DNA methylation with paralog evolution. Genic DNA methylation was differentially associated with duplication type, the age of duplication, sequence evolution, and gene expression. Whole-genome duplicates were typically enriched for CG-only gene body methylated or unmethylated genes, while single-gene duplications were typically enriched for non-CG methylated or unmethylated genes. Non-CG methylation, in particular, was a characteristic of more recent single-gene duplicates. Core angiosperm gene families were differentiated into those which preferentially retain paralogs and “duplication-resistant” families, which convergently reverted to singletons following duplication. Duplication-resistant families that still have paralogous copies were, uncharacteristically for core angiosperm genes, enriched for non-CG methylation. Non-CG methylated paralogs had higher rates of sequence evolution, higher frequency of presence–absence variation, and more limited expression. This suggests that silencing by non-CG methylation may be important to maintaining dosage following duplication and be a precursor to fractionation. Our results indicate that genic methylation marks differing evolutionary trajectories and fates between paralogous genes and have a role in maintaining dosage following duplication.
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Epigenetic diversity of genes with copy number variations among natural populations of the three‐spined stickleback
Abstract Duplicated genes provide the opportunity for evolutionary novelty and adaptive divergence. In many cases, having more gene copies increases gene expression, which might facilitate adaptation to stressful or novel environments. Conversely, overexpression or misexpression of duplicated genes can be detrimental and subject to negative selection. In this scenario, newly duplicate genes may evade purifying selection if they are epigenetically silenced, at least temporarily, leading them to persist in populations as copy number variations (CNVs). In animals and plants, younger gene duplicates tend to have higher levels of DNA methylation and lower levels of gene expression, suggesting epigenetic regulation could promote the retention of gene duplications via expression repression or silencing. Here, we test the hypothesis that DNA methylation variation coincides with young duplicate genes that are segregating as CNVs in six populations of the three‐spined stickleback that span a salinity gradient from 4 to 30 PSU. Using reduced‐representation bisulfite sequencing, we found DNA methylation and CNV differentiation outliers rarely overlapped. Whereas lineage‐specific genes and young duplicates were found to be highly methylated, just two gene CNVs showed a significant association between promoter methylation level and copy number, suggesting that DNA methylation might not interact with CNVs in our dataset. If most new duplications are regulated for dosage by epigenetic mechanisms, our results do not support a strong contribution from DNA methylation soon after duplication. Instead, our results are consistent with a preference to duplicate genes that are already highly methylated.
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- Award ID(s):
- 2144259
- PAR ID:
- 10577649
- Publisher / Repository:
- John Wiley & Sons Ltd.
- Date Published:
- Journal Name:
- Evolutionary Applications
- Volume:
- 17
- Issue:
- 7
- ISSN:
- 1752-4571
- Subject(s) / Keyword(s):
- adaptive differentiation copy number variations (CNVs) DNA methylation epigenetic regulation gene duplication stickleback
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Wittkopp, Patricia (Ed.)Abstract Whole-genome duplications (WGDs) have occurred in many eukaryotic lineages. However, the underlying evolutionary forces and molecular mechanisms responsible for the long-term retention of gene duplicates created by WGDs are not well understood. We employ a population-genomic approach to understand the selective forces acting on paralogs and investigate ongoing duplicate-gene loss in multiple species of Paramecium that share an ancient WGD. We show that mutations that abolish protein function are more likely to be segregating in retained WGD paralogs than in single-copy genes, most likely because of ongoing nonfunctionalization post-WGD. This relaxation of purifying selection occurs in only one WGD paralog, accompanied by the gradual fixation of nonsynonymous mutations and reduction in levels of expression, and occurs over a long period of evolutionary time, “marking” one locus for future loss. Concordantly, the fitness effects of new nonsynonymous mutations and frameshift-causing indels are significantly more deleterious in the highly expressed copy compared with their paralogs with lower expression. Our results provide a novel mechanistic model of gene duplicate loss following WGDs, wherein selection acts on the sum of functional activity of both duplicate genes, allowing the two to wander in expression and functional space, until one duplicate locus eventually degenerates enough in functional efficiency or expression that its contribution to total activity is too insignificant to be retained by purifying selection. Retention of duplicates by such mechanisms predicts long times to duplicate-gene loss, which should not be falsely attributed to retention due to gain/change in function.more » « less
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Summary Polyploidy is an important evolutionary force, yet epigenetic mechanisms, such as DNA methylation, that regulate genome‐wide expression of duplicated genes remain largely unknown. Here, we useTragopogon(Asteraceae) as a model system to discover patterns and temporal dynamics of DNA methylation in recently formed polyploids.The naturally occurring allotetraploidTragopogon miscellusformed in the last 95–100 yr from parental diploidsTragopogon dubiusandT. pratensis. We profiled the DNA methylomes of these three species using whole‐genome bisulfite sequencing.Genome‐wide methylation levels inT. miscelluswere intermediate between its diploid parents. However, nonadditive CG and CHG methylation occurred in transposable elements (TEs), with variation among TE types. Most differentially methylated regions (DMRs) showed parental legacy, but some novel DMRs were detected in the polyploid. Differentially methylated genes (DMGs) were also identified and characterized.This study provides the first assessment of both overall and locus‐specific patterns of DNA methylation in a recent natural allopolyploid and shows that novel methylation variants can be generated rapidly after polyploid formation. Together, these results demonstrate that mechanisms to regulate duplicate gene expression may arise soon after allopolyploid formation and that these mechanisms vary among genes.more » « less
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Abstract The duplication of genes has long been recognized as a substrate for evolutionary novelty and adaptation, but the factors that govern fixation of paralogs soon after duplication are only partially understood. Duplication often leads to an increase in gene dosage, or the amount of functional gene product. For genes with which an increased dosage is harmful (i.e., triplosensitive genes), a dosage balancing mechanism needs to be present immediately after duplication if it is to evade negative selection. Previous research in vertebrates has demonstrated a potential role for epigenetic factors in allowing triplosensitive genes to increase in copy number by regulating their expression post-duplication. Here we expand this research by investigating the epigenetic landscape of duplicate genes inD. discoideum, a basal lineage separated from humans by over a billion years. We found that activating histone modifications are quickly lost in duplicate genes before gradually increasing in enrichment as paralogs age. For the repressive modification H3K9me3, we found it was enriched in the youngest paralogs, and that this enrichment was likely mediated by heterochromatin spread from transposable elements. We similarly found enrichment of H3K9me3 in young human duplicates, and again found transposable elements as a potential mediator. Finally, we leveraged recent genome-wide estimates of triplosensitivity in human genes to directly examine the relationship between this kind of dosage sensitivity and enrichment for repressive histone modifications. Interestingly, while we found no significant link between enrichment for the repressive mark H3K9me3 and triplosensitivity in human paralogs, we did find a significant association between triplosensitivity and transposon proximity. Our findings suggest that transposons may contribute to the epigenetic regulatory environment associated with dosage balancing of young duplicates in both protists and humans.more » « less
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1111/eva.13753
