Hypermutable Sites Are under Stronger Selection
Author Information
Author(s): Schmidt Steffen, Gerasimova Anna, Kondrashov Fyodor A., Adzuhbei Ivan A., Kondrashov Alexey S., Sunyaev Shamil
Primary Institution: Brigham and Women's Hospital, Harvard Medical School
Hypothesis
There may be a positive correlation between the rate of mutations at a nucleotide site and the magnitude of their effect on fitness.
Conclusion
Highly mutable nucleotide sites, such as the dinucleotide CpG, are on average more important and more frequently preserved by natural selection.
Supporting Evidence
- The study found that the probability of fixation of a non-synonymous transition at a CpG site is two times lower than at a non-CpG site.
- Nucleotides within CpG context are under stronger negative selection, as indicated by their lower rate of evolution and nucleotide diversity.
- The impact of CpG context on the rate of divergence was found to be significantly higher for transitions than for transversions.
Takeaway
Some parts of our DNA change more often than others, and those changes can be more important for how we function. This study found that certain frequently changing sites are often kept because they are important.
Methodology
The study analyzed human-chimpanzee-orangutan alignments to compare mutation rates and selection strength at non-synonymous coding sites within and outside CpG contexts.
Potential Biases
Potential misidentification of ancestral alleles could lead to underestimation of the impact of CpG context.
Limitations
The estimates of the impact of CpG context on divergence may be too low due to substitutions in the outgroup lineage.
Statistical Information
P-Value
p<2.8·10−16
Statistical Significance
p<2.8·10−16
Digital Object Identifier (DOI)
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