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Diverse selective regimes shape genetic diversity at ADAR genes and at their coding targets
- Publication Year :
- 2015
- Publisher :
- Taylor & Francis, 2015.
-
Abstract
- A-to-I RNA editing operated by ADAR enzymes is extremely common in mammals. Several editing events in coding regions have pivotal physiological roles and affect protein sequence (recoding events) or function. We analyzed the evolutionary history of the 3 ADAR family genes and of their coding targets. Evolutionary analysis indicated that ADAR evolved adaptively in primates, with the strongest selection in the unique N-terminal domain of the interferon-inducible isoform. Positively selected residues in the human lineage were also detected in the ADAR deaminase domain and in the RNA binding domains of ADARB1 and ADARB2. During the recent history of human populations distinct variants in the 3 genes increased in frequency as a result of local selective pressures. Most selected variants are located within regulatory regions and some are in linkage disequilibrium with eQTLs in monocytes. Finally, analysis of conservation scores of coding editing sites indicated that editing events are counter-selected within regions that are poorly tolerant to change. Nevertheless, a minority of recoding events occurs at highly conserved positions and possibly represents the functional fraction. These events are enriched in pathways related to HIV-1 infection and to epidermis/hair development. Thus, both ADAR genes and their targets evolved under variable selective regimes, including purifying and positive selection. Pressures related to immune response likely represented major drivers of evolution for ADAR genes. As for their coding targets, we suggest that most editing events are slightly deleterious, although a minority may be beneficial and contribute to antiviral response and skin homeostasis.
- Subjects :
- Primates
Adenosine Deaminase
Molecular Sequence Data
Quantitative Trait Loci
RNA-binding protein
Sequence alignment
RNA-Binding Protein
Biology
Monocyte
Monocytes
Linkage Disequilibrium
Open Reading Frame
Open Reading Frames
Animals
Humans
A-to-I editing
Coding region
Amino Acid Sequence
Selection, Genetic
Codon
Molecular Biology
Gene
Skin
Genetics
Sequence Homology, Amino Acid
Animal
Primate
RNA-Binding Proteins
Genetic Variation
Cell Biology
Research Papers
ADAR
Biological Evolution
Isoenzyme
Isoenzymes
Positive selection
ADAR editing site
Regulatory sequence
RNA editing
Evolutionary analysi
RNA Editing
Sequence Alignment
Function (biology)
Hair
Human
Subjects
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....b83886e5e14bef3a21d012a727155462
- Full Text :
- https://doi.org/10.6084/m9.figshare.1378747.v1