title: The preferred nucleotide contexts of the AID/APOBEC cytidine deaminases have differential effects when mutating retrotransposon and virus sequences compared to host genes.
abstract: The AID / APOBEC genes are a family of cytidine deaminases that have evolved in vertebrates, and particularly mammals, to mutate RNA and DNA at distinct preferred nucleotide contexts (or "hotspots") on foreign genomes such as viruses and retrotransposons. These enzymes play a pivotal role in intrinsic immunity defense mechanisms, often deleteriously mutating invading retroviruses or retrotransposons and, in the case of AID, changing antibody sequences to drive affinity maturation. We investigate the strength of various hotspots on their known biological targets by evaluating the potential impact of mutations on the DNA coding sequences of these targets, and compare these results to hypothetical hotspots that did not evolve. We find that the existing AID / APOBEC hotspots have a large impact on retrotransposons and non-mammalian viruses while having a much smaller effect on vital mammalian genes, suggesting co-evolution with AID / APOBECs may have had an impact on the genomes of the viruses we analyzed. We determine that GC content appears to be a significant, but not sole, factor in resistance to deaminase activity. We discuss possible mechanisms AID and APOBEC viral targets have adopted to escape the impacts of deamination activity, including changing the GC content of the genome.
authors.affiliation: Department of Applied Mathematics and Statistics, Stony Brook University, Stony Book, New York, United States of America.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Applied Mathematics and Statistics, Stony Brook University, Stony Book, New York, United States of America.
authors.forename: Thomas
authors.identifier: 0000-0003-0025-9285
authors.initials: T
authors.lastname: MacCarthy
mesh_terms: D000071478:APOBEC Deaminases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020816:Amino Acid Motifs; D000818:Animals; D001482:Base Composition; D003062:Codon; D019295:Computational Biology; D016679:Genome, Viral; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D018626:Retroelements / Q000235:genetics; D012190:Retroviridae / Q000235:genetics
chemical_list: D003062:Codon; D018626:Retroelements; D000071478:APOBEC Deaminases