An ancient history of gene duplications, fusions and losses in the evolution of APOBEC3 mutators in mammals
The APOBEC3 (A3) genes play a key role in innate antiviral defense in mammals by introducing directed mutations in the DNA. The human genome encodes for seven A3 genes, with multiple splice alternatives. Different A3 proteins display different substrate specificity, but the very basic question on how discerning self from non-self still remains unresolved. Further, the expression of A3 activity/ies shapes the way both viral and host genomes evolve.
We present here a detailed temporal analysis of the origin and expansion of the A3 repertoire in mammals. Our data support an evolutionary scenario where the genome of the mammalian ancestor encoded for at least one ancestral A3 gene, and where the genome of the ancestor of placental mammals (and possibly of the ancestor of all mammals) already encoded for an A3Z1-A3Z2-A3Z3 arrangement. Duplication events of the A3 genes have occurred independently in different lineages: humans, cats and horses. In all of them, gene duplication has resulted in changes in enzyme activity and/or substrate specificity, in a paradigmatic example of convergent adaptive evolution at the genomic level. Finally, our results show that evolutionary rates for the three A3Z1, A3Z2 and A3Z3 motifs have significantly decreased in the last 100 Mya. The analysis constitutes a textbook example of the evolution of a gene locus by duplication and sub/neofunctionalization in the context of virus-host arms race.
Our results provide a time framework for identifying ancestral and derived genomic arrangements in the APOBEC loci, and to date the expansion of this gene family for different lineages through time, as a response to changes in viral/retroviral/retrotransposon pressure.
- blah 12862_2012_2105_MOESM1_ESM.xls (47KB)
- blah 12862_2012_2105_MOESM2_ESM.png (294KB)
- blah 12862_2012_2105_MOESM3_ESM.png (1374KB)
- blah 12862_2012_2105_MOESM4_ESM.png (49KB)
- blah 12862_2012_2105_MOESM5_ESM.xls (23KB)
- blah 12862_2012_2105_MOESM6_ESM.png (123KB)
- blah 12862_2012_2105_MOESM7_ESM.txt (376KB)
- An ancient history of gene duplications, fusions and losses in the evolution of APOBEC3 mutators in mammals
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
BMC Evolutionary Biology
- Online Date
- May 2012
- Online ISSN
- BioMed Central
- Additional Links
- Cytydine deaminase
- Gene duplication
- Virus/host arms race
- Author Affiliations
- 1. Clinic for Gastroenterology, Hepatology and Infectiology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany
- 2. Genomics and Health, Centre for Public Health Research (CSISP), Valencia, Spain
- 3. Infections and Cancer, Catalan Institute of Oncology (ICO) | Bellvitge Institute of Biomedical Research (IDIBELL), Barcelona, Spain
- 4. Infections and Cancer, Catalan Institute of Oncology (ICO), L’Hospitalet de Llobregat, Avda. Gran Via, 199-203, Barcelona, 08908, Spain