Evolution of the AID/APOBEC Family of Polynucleotide (Deoxy)cytidine Deaminases

Authors: Conticello, Silvestro G.; Thomas, Cornelia J. F.; Neuberger, Michael S.

Source: Molecular Biology and Evolution, Volume 22, Number 2, February 2005 , pp. 367-377(11)

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Abstract:

The AID/APOBEC family (comprising AID, APOBEC1, APOBEC2, and APOBEC3 subgroups) contains members that can deaminate cytidine in RNA and/or DNA and exhibit diverse physiological functions (AID and APOBEC3 deaminating DNA to trigger pathways in adaptive and innate immunity; APOBEC1 mediating apolipoprotein B RNA editing). The founder member APOBEC1, which has been used as a paradigm, is an RNA-editing enzyme with proposed antecedents in yeast. Here, we have undertaken phylogenetic analysis to glean insight into the primary physiological function of the AID/APOBEC family. We find that although the family forms part of a larger superfamily of deaminases distributed throughout the biological world, the AID/APOBEC family itself is restricted to vertebrates with homologs of AID (a DNA deaminase that triggers antibody gene diversification) and of APOBEC2 (unknown function) identifiable in sequence databases from bony fish, birds, amphibians, and mammals. The cloning of an AID homolog from dogfish reveals that AID extends at least as far back as cartilaginous fish. Like mammalian AID, the pufferfish AID homolog can trigger deoxycytidine deamination in DNA but, consistent with its cold-blooded origin, is thermolabile. The fine specificity of its mutator activity and the biased codon usage in pufferfish IgV genes appear broadly similar to that of their mammalian counterparts, consistent with a coevolution of the antibody mutator and its substrate for the optimal targeting of somatic mutation during antibody maturation. By contrast, APOBEC1 and APOBEC3 are later evolutionary arrivals with orthologs not found in pufferfish (although synteny with mammals is maintained in respect of the flanking loci). We conclude that AID and APOBEC2 are likely to be the ancestral members of the AID/APOBEC family (going back to the beginning of vertebrate speciation) with both APOBEC1 and APOBEC3 being mammal-specific derivatives of AID and a complex set of domain shuffling underpinning the expansion and evolution of the primate APOBEC3s.

Keywords: AID; APOBEC; antibody gene diversification; hypermutation; RNA editing; DNA deamination; immunity

Document Type: Research article

DOI: http://dx.doi.org/10.1093/molbev/msi026

Publication date: 2005-02-01

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Molecular Biology and Evolution publishes research at the interface between molecular and evolutionary biology. The journal publishes investigations of molecular evolutionary patterns and processes, tests of evolutionary hypotheses that use molecular data, and studies that use molecular evolutionary information to address questions about biological function at all levels of organization.

Evolution of the AID/APOBEC Family of Polynucleotide (Deoxy)cytidine Deaminases

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