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Problems and solutions for estimating indel rates and length distributions.

Reed A Cartwright1

  • 1Department of Genetics, Bioinformatics Research Center, North Carolina State University, Raleigh, NC, USA. racartwr@ncsu.edu

Molecular Biology and Evolution
|December 2, 2008
PubMed
Summary

We developed a new algorithm to accurately analyze insertions and deletions (indels) in DNA, revealing that a power-law model better describes indel lengths than traditional models.

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Area of Science:

  • Molecular Evolution
  • Genomics
  • Bioinformatics

Background:

  • Insertions and deletions (indels) are crucial but understudied aspects of molecular evolution.
  • Traditional models for analyzing indels may introduce artifacts into evolutionary studies.

Purpose of the Study:

  • To develop and present an expectation-maximization algorithm using a pair hidden Markov model to accurately handle indels in neutral DNA sequences.
  • To estimate indel rates and length distributions in primates and rodents.
  • To compare the fit of different indel length models.

Main Methods:

  • Developed an expectation-maximization algorithm based on a pair hidden Markov model.
  • Analyzed orthologous introns from primates and rodents.
  • Estimated relative indel rates and length distributions.

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  • Compared zeta power-law and geometric models for indel lengths.

    • Main Results:

    • A zeta power-law model significantly outperforms the traditional geometric model in describing indel lengths.
    • Indel processes appear conserved across primates and rodents.
    • Estimated relative indel rates are 12-16 indels per 100 substitutions.
    • Estimated power-law magnitudes are approximately 1.6-1.7.
    • Traditional geometric/affine models introduce artifacts into evolutionary analyses.

    Conclusions:

    • The new algorithm accurately handles indels in neutral DNA sequences.
    • The zeta power-law model is superior for modeling indel lengths.
    • Traditional models may lead to inaccurate conclusions regarding indel evolution and species divergence.