Both authors contributed equally to this work.
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Research Article
More single-nucleotide mutations surround small insertions than small deletions in primates†
Article first published online: 9 APR 2012
DOI: 10.1002/humu.22085
© 2012 Wiley Periodicals, Inc.
Additional Information
How to Cite
Huang, S., Yu, T., Chen, Z., Yuan, S., Chen, S. and Xu, A. (2012), More single-nucleotide mutations surround small insertions than small deletions in primates. Hum. Mutat., 33: 1099–1106. doi: 10.1002/humu.22085
- †
Communicated by David N. Cooper
- ‡
Both authors contributed equally to this work.
Publication History
- Issue published online: 5 JUN 2012
- Article first published online: 9 APR 2012
- Accepted manuscript online: 27 MAR 2012 09:44AM EST
- Manuscript Accepted: 6 MAR 2012
- Manuscript Received: 1 NOV 2011
Funded by
- Project. Grant Number: 2008AA092600 (863)
- National Natural Science Foundation of China. Grant Number: Projects 31171193, 30901103, and 30730089
- National Basic Research Program. Grant Number: 2011CB946101 [973]
- Commission of Science and Technology of Guangdong Province and Guangzhou City; Sun Yat-sen Univeristy Science Foundation
Keywords:
- insertion;
- deletion;
- selection;
- human population;
- primate;
- genome;
- single-nucleotide mutation
Abstract
Early studies have shown that single-nucleotide mutation rates increase close to insertions and deletions, but it is not fully understood how natural selection shapes genome-wide patterns of indels and their nearby single-nucleotide mutations. In this study, we find that, in primates, more single-nucleotide mutations surround small insertions than small deletions. This pattern affects <150 base pair (bp) sequences close to indels and persists under different genomic properties, such as exon/intron/intergenic contexts, repeated/nonrepeated sequences, replication timing, recombination rates, indel density, and guanine–cytosine (GC) content. We propose two different, but not mutually exclusive, hypothetical mechanisms to explain the pattern. One mechanism is that the sequence context preferring insertion formation may also favor nucleotide substitutions. Another mechanism is related to a hypothesis in which indel heterozygosity tends to increase nearby nucleotide substitution rates. It means that if insertions spend more time in heterozygotes, insertions may accumulate more surrounding single-nucleotide changes. In conclusion, we characterize a special genome-wide evolutionary pattern for indels and nearby single-nucleotide changes. This pattern may be driven by natural selection and bias primates' genome evolution and phenotypic variations. Hum Mutat 33:1099–1106, 2012. © 2012 Wiley Periodicals, Inc.