Epigenetic silencing and genome dynamics determine the fate of giant virus endogenizations in Acanthamoeba

Endogenized giant viruses are emerging as major contributors to the genome evolution of microbial eukaryotes, with both degraded and fully functional latent viruses being found integrated in diverse lineages. The mechanisms that determine the fate of viral integrants are poorly understood, however. Acanthamoeba is a unicellular eukaryote known for undergoing lateral gene transfer (LGT) with viruses. Here we have leveraged chromosome-scale assemblies of two strains of Acanthamoeba, Neff and C3, to investigate the genomic mechanisms that mediate the fate of viral integrations in eukaryotic genomes.

Viral integrations in the C3 and Neff genomes are largely non-overlapping and disproportionately found in sub-telomeric regions. Multiple partial copies of these insertions are found throughout the Neff genome, but they are not expressed, do not obviously encode functions associated with their own mobility, and are colonized by host mobile elements. Viral regions are hypermethylated and highly condensed, suggesting that the expression of recently acquired viral DNA is suppressed in heterochromatic regions.

We propose a model for the trajectory of viral sequences in Acanthamoeba: (i) integration of DNA from giant viruses, (ii) epigenetic suppression of the viral DNAs, allowing them to persist in the genome, and (iii) deterioration of viral genomes by point mutation, mobile element colonization, 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 amoeba. Our work highlights the importance of host genome dynamics and epigenetic silencing for understanding the evolution of endogenized viral elements.