Effect of the assignment of ancestral CpG state on the estimation of nucleotide substitution rates in mammals
2008

Impact of Ancestral CpG State on Nucleotide Substitution Rates in Mammals

Sample size: 1470 publication Evidence: high

Author Information

Author(s): Daniel J Gaffney, Peter D Keightley

Primary Institution: McGill University and Genome Québec Innovation Centre

Hypothesis

How does the assignment of ancestral CpG state affect the estimation of nucleotide substitution rates in mammals?

Conclusion

The study shows that a common method of assigning nucleotide sites to CpG and non-CpG classes is seriously biased.

Supporting Evidence

  • The assignment of ancestral CpG state can seriously bias estimates of substitution rates.
  • Bias is most severe between closely related species.
  • Fourfold degenerate sites can appear to evolve more slowly than noncoding sites due to misassignment.
  • The study demonstrates that the predicted effects occur in real evolutionary settings.
  • CpG/non-CpG assignment can lead to underestimation of non-CpG substitution rates.

Takeaway

This study found that the way we categorize DNA sites can lead to big mistakes in understanding how fast DNA changes over time.

Methodology

Simulations of DNA sequence evolution were used to analyze the effects of CpG/non-CpG assignment on substitution rates.

Potential Biases

The method of assigning ancestral states can lead to significant misclassification of nucleotide changes.

Limitations

The study primarily focuses on closely related species and may not generalize to more distantly related species.

Statistical Information

P-Value

<0.0001

Confidence Interval

(0.0058,0.0064)

Statistical Significance

p<0.0001

Digital Object Identifier (DOI)

10.1186/1471-2148-8-265

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