A survey of genomic traces reveals a common sequencing error, RNA editing, and DNA editing.
While it is widely held that an organism's genomic information should remain constant, several protein families are known to modify it. Members of the AID/APOBEC protein family can deaminate DNA. Similarly, members of the ADAR family can deaminate RNA. Characterizing the scope of these events is challenging. Here we use large genomic data sets, such as the two billion sequences in the NCBI Trace Archive, to look for clusters of mismatches of the same type, which are a hallmark of editing events caused by APOBEC3 and ADAR. We align 603,249,815 traces from the NCBI trace archive to their reference genomes. In clusters of mismatches of increasing size, at least one systematic sequencing error dominates the results (G-to-A). It is still present in mismatches with 99% accuracy and only vanishes in mismatches at 99.99% accuracy or higher. The error appears to have entered into about 1% of the HapMap, possibly affecting other users that rely on this resource. Further investigation, using stringent quality thresholds, uncovers thousands of mismatch clusters with no apparent defects in their chromatograms. These traces provide the first reported candidates of endogenous DNA editing in human, further elucidating RNA editing in human and mouse and also revealing, for the first time, extensive RNA editing in Xenopus tropicalis. We show that the NCBI Trace Archive provides a valuable resource for the investigation of the phenomena of DNA and RNA editing, as well as setting the stage for a comprehensive mapping of editing events in large-scale genomic datasets.
Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America. await@genetics.med.harvard.edu
Alexander Wait
AW
Zaranek
Erez Y
EY
Levanon
Tomer
T
Zecharia
Tom
T
Clegg
George M
GM
Church
D000071478:APOBEC Deaminases; D000243:Adenosine Deaminase / Q000235:genetics; D020137:Base Pair Mismatch; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000235:genetics; D004247:DNA / Q000235:genetics*; D023281:Genomics; D006801:Humans; D005810:Multigene Family; D017393:RNA Editing; D016601:RNA-Binding Proteins
D016601:RNA-Binding Proteins; D004247:DNA; D043525:Cytosine Deaminase; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase