Biology subjects

Sarre, L. A.

Publications and source records attributed to Sarre, L. A..

5 recordsLinked to original sources

bioRxiv2025

Cytosine Methylation is a marker of Viral Gene Transfer across the eukaryotes

Cytosine DNA methylation patterns vary widely across eukaryotes, with its ancestral roles being understood to have included both transposable element silencing and host gene regulation. To further explore these claims, in this study, we reevaluate the evolutionary origins of DNA methyltransferases and characterise the roles of cytosine methylation on underexplored lineages, including the amoebozoan Acanthamoeba castellanii, the glaucophyte Cyanophora paradoxa, and the heterolobosean Naegleria gruberi. Our analysis of DNA methyltransferase evolution reveals a rich ancestral eukaryotic repertoire, with several eukaryotic lineages likely subsequently acquiring enzymes through lateral gene transfer (LGT). In the three species examined, DNA methylation is enriched on young transposable elements and silenced genes, suggesting an ancestral repressive function, without the transcription-linked gene body methylation of plants and animals. Notably, the closest homologues of many of the silenced, methylated genes in diverse eukaryotes belong to viruses, including giant viruses. Given the widespread occurrence of this pattern across diverse eukaryotic groups, we propose that cytosine methylation was a silencing mechanism originally acquired from bacterial donors which was used to mitigate the expression of both transposable and viral elements, and that this function may persist in creating a permissive atmosphere for LGT in diverse eukaryotic lineages. These findings further highlight the importance of epigenetic information to annotate eukaryotic genomes, as it helps delimit potentially adaptive LGTs from silenced parasitic elements.

genomics↗

bioRxiv2024

Epigenetic silencing and host genome evolution determine fate of viral insertions in Acanthamoeba

Acanthamoeba is a cosmopolitan freshwater amoebae known for its association with Nucleocytoplasmic Large DNA Viruses (NCLDVs). Previous studies have shown that Acanthamoeba spp. undergo lateral gene transfer (LGT) with NCLDVs. Here we have leveraged chromosome-scale assemblies of two strains of Acanthamoeba castellanii, Neff and C3, to investigate the occurrence and genomic context of viral LGT in Acanthamoeba. We show that the viral footprints in the C3 and Neff genomes are largely non-overlapping and that viral genes in Neff are found disproportionately in large sub-telomeric insertions. Multiple partial copies of these insertions are found throughout the Neff genome, but they are not expressed and do not encode functions for their own mobility. Viral regions are hyper-methylated and highly condensed, suggesting that the expression of recently acquired viral DNA is suppressed in heterochromatic regions. We propose a three-step model for the origin and fate of viral sequences in Acanthamoeba: (i) integration of DNA from giant viruses, (ii) epigenetic suppression of the viral DNAs, which allows them to persist in the genome, and (iii) deterioration of viral genomes by point mutation and intra- and inter-chromosomal recombination. Viral integrations in Acanthamoeba spp. are transient and may not have long-lasting effects on the fitness of the host amoeba. Our work strengthens a growing body of work showing widespread but transient integration of viral DNA in protists and extends the relevance of epigenetic silencing mechanisms to the evolution of Amoebozoa. We highlight the importance of host genome dynamics for understanding the evolution of endogenized viral elements.

genomics↗

bioRxiv2024

Adenine DNA methylation associated to transcription is widespread across eukaryotes

DNA methylation in the form of 5-methylcytosine (5mC) is widespread in eukaryotes, while the presence of N6-methyladenine (6mA) has sparked considerable debate. Methodological disparities in quantifying and mapping 6mA in genomic DNA have fueled this controversy. Yet, the distantly related early branching fungi, ciliates and the algae Chlamydomonas reinhardtii exhibit robust 6mA methylation patterns, but the origin and evolution of 6mA remain unknown. Here we use Oxford Nanopore modified base calling to profile 6mA at base pair resolution in 18 unicellular eukaryotes spanning all major eukaryotic supergroups. Our results reveal that only species encoding the adenine methyltransferase AMT1 display robust genomic 6mA patterns. Notably, 6mA consistently accumulates downstream of transcriptional start sites, aligning with H3K4me3-enriched nucleosomes, suggesting a conserved role in placing transcriptionally permissive nucleosomes. Intriguingly, the recurrent loss of the 6mA pathway across eukaryotes, particularly in major multicellular lineages, implies a convergent alteration in the dual methylation system of the Last Eukaryotic Common Ancestor, which featured transcription-associated 6mA and repression-associated 5mC.

genomics↗

bioRxiv2024

DNA methylation enables recurrent endogenization of giant viruses in an animal relative

5-methylcytosine (5mC) is a widespread silencing mechanism that controls genomic parasites. However, in many eukaryotes 5mC has gained complex roles in gene regulation beyond parasite control. Animals are a quintessential case for 5mC evolution, as they show widespread variability across lineages, ranging from gene regulation and transposable element control to loss of this base modification. Here we show that the protist closely related to animals Amoebidium appalachense features both transposon and gene body methylation, a pattern reminiscent of invertebrates and plants. Unexpectedly, large hypermethylated regions of the Amoebidium genome derive from viral insertions, including hundreds of endogenized giant viruses contributing 14% of the encoded genes, to an extent never reported before in any eukaryotic genome. Using a combination of inhibitors and functional genomic assays, we demonstrate that 5mC silences these giant virus insertions. Moreover, alternative Amoebidium isolates show polymorphic giant virus insertions, highlighting a dynamic process of infection, endogenization and purging. Our results indicate that 5mC is critical for the controlled co-existence of newly acquired viral DNA into eukaryotic genomes, making Amoebidium a unique model to understand the hybrid origins of eukaryotic genomes.

evolutionary biology↗

bioRxiv2023

Annelid methylomes reveal ancestral developmental and ageing-associated epigenetic erosion across Bilateria

BackgroundDNA methylation in the form of 5-methylcytosine (5mC) is the most abundant base modification in animals. However, 5mC levels vary widely across taxa. While vertebrate genomes are hypermethylated, in most invertebrates, 5mC concentrates on constantly and highly transcribed genes (gene body methylation; GbM) and, in some species, on transposable elements (TEs), a pattern known as mosaic. Yet, the role and developmental dynamics of 5mC and how these explain interspecific differences in DNA methylation patterns remain poorly understood, especially in Spiralia, a large clade of invertebrates comprising nearly half of the animal phyla. ResultsHere, we generate base-resolution methylomes for three species with distinct genomic features and phylogenetic positions in Annelida, a major spiralian phylum. All possible 5mC patterns occur in annelids, from typical invertebrate intermediate levels in a mosaic distribution to hypermethylation and methylation loss. GbM is common to annelids with 5mC, and methylation differences across species are explained by taxon-specific transcriptional dynamics or the presence of intronic TEs. Notably, the link between GbM and transcription decays during development, and there is a gradual and global, age-dependent demethylation in adult stages. Moreover, reducing 5mC levels with cytidine analogues during early development impairs normal embryogenesis and reactivates TEs in the annelid Owenia fusiformis. ConclusionsOur study indicates that global epigenetic erosion during development and ageing is an ancestral feature of bilateral animals. However, the tight link between transcription and gene body methylation is likely important in early embryonic stages, and 5mC-mediated TE silencing probably emerged convergently across animal lineages.

genomics↗