journal.pbio.1000027.pdf (258.6 kB)
Cryptic Variation in the Human Mutation Rate
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posted on 2023-06-08, 06:52 authored by Alan Hodgkinson, Emmanuel Ladoukakis, Adam Eyre-WalkerAdam Eyre-WalkerThe mutation rate is known to vary between adjacent sites within the human genome as a consequence of context, the most well-studied example being the influence of CpG dinucelotides. We investigated whether there is additional variation by testing whether there is an excess of sites at which both humans and chimpanzees have a single-nucleotide polymorphism ( SNP). We found a highly significant excess of such sites, and we demonstrated that this excess is not due to neighbouring nucleotide effects, ancestral polymorphism, or natural selection. We therefore infer that there is cryptic variation in the mutation rate. However, although this variation in the mutation rate is not associated with the adjacent nucleotides, we show that there are highly nonrandom patterns of nucleotides that extend similar to 80 base pairs on either side of sites with coincident SNPs, suggesting that there are extensive and complex context effects. Finally, we estimate the level of variation needed to produce the excess of coincident SNPs and show that there is a similar, or higher, level of variation in the mutation rate associated with this cryptic process than there is associated with adjacent nucleotides, including the CpG effect. We conclude that there is substantial variation in the mutation that has, until now, been hidden from view.
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- Published
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- Published version
Journal
PLoS BiologyISSN
1544-9173External DOI
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2Volume
7Article number
e1000027Pages
7.0Department affiliated with
- Evolution, Behaviour and Environment Publications
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- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06First Open Access (FOA) Date
2016-03-22First Compliant Deposit (FCD) Date
2016-11-10Usage metrics
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