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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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Molecular evolution of the ependymin-related gene epdl2 in African weakly electric fish
Abstract Gene duplication and subsequent molecular evolution can give rise to taxon-specific gene specializations. In previous work, we found evidence that African weakly electric fish (Mormyridae) may have as many as three copies of the epdl2 gene, and the expression of two epdl2 genes is correlated with electric signal divergence. Epdl2 belongs to the ependymin-related family (EPDR), a functionally diverse family of secretory glycoproteins. In this study, we first describe vertebrate EPDR evolution and then present a detailed evolutionary history of epdl2 in Mormyridae with emphasis on the speciose genus Paramormyrops. Using Sanger sequencing, we confirm three apparently functional epdl2 genes in Paramormyrops kingsleyae. Next, we developed a nanopore-based amplicon sequencing strategy and bioinformatics pipeline to obtain and classify full-length epdl2 gene sequences (N = 34) across Mormyridae. Our phylogenetic analysis proposes three or four epdl2 paralogs dating from early Paramormyrops evolution. Finally, we conducted selection tests which detected positive selection around the duplication events and identified ten sites likely targeted by selection in the resulting paralogs. These sites’ locations in our modeled 3D protein structure involve four sites in ligand binding and six sites in homodimer formation. Together, these findings strongly imply an evolutionary mechanism whereby epdl2 genes underwent selection-driven functional specialization after tandem duplications in the rapidly speciating Paramormyrops. Considering previous evidence, we propose that epdl2 may contribute to electric signal diversification in mormyrids, an important aspect of species recognition during mating.
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- PAR ID:
- 10484196
- Editor(s):
- McCallion, A
- Publisher / Repository:
- Oxford
- Date Published:
- Journal Name:
- G3 Genes|Genomes|Genetics
- Volume:
- 13
- Issue:
- 3
- ISSN:
- 2160-1836
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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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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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1093/g3journal/jkac331
