Ancient eukaryotic immunity through genome editing of viral sequences

Abstract

Mutations provide the raw material for evolution, but mutation rates are not uniform across genomes. Using a mutation accumulation experiment in the marine phytoplankton Bigelowiella natans, we discovered extreme local variation in mutation rate: over 1000-fold differences across its nuclear genome. While the baseline single-nucleotide mutation rate is approximately 3.5x10-10 per site per generation, a common value for unicellular species, two genomic regions derived from integrated viruses exhibit strikingly elevated rates of about 6x10-7. These two regions show a distinctive mutational signature with almost exclusively T/A[->]C/G transitions, a pattern also found in other non-eukaryote derived sequences in B. natans, contrary to the usual GC to AT mutation bias. Notably, hypermutation occurs only on TpA dinucleotides, and only in a subset of experimental lines, suggesting a regulated process rather than random genomic instability. We propose that B. natans targets invading DNA through localized hypermutation, reminiscent of deamination-based antiviral defense systems in animals, prompting the idea of genome editing as a conserved immune system in eukaryotes. Significance StatementDe novo mutations provide the raw material for adaptation, but at high frequencies they can compromise genome integrity. Here, we describe a hypermutable process targeting two integrated viral genomes in a chlorarachniophyte alga, resulting in a mutation rate 1000 times higher than in other regions and a very particular mutation spectrum. These observations are reminiscent of hypermutation-based antiviral defenses described in humans against HIV and influenza; whereby host-mediated deamination of the viral genome increases its mutation rate such that the virus loses its infectivity.