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The inference of stepwise changes in substitution rates using serial sequence samples.

A Drummond1, R Forsberg, A G Rodrigo

  • 1School of Biological Sciences, University of Auckland, Auckland, New Zealand. Department of Ecology and Genetics, University of Arhus, Arhus, Denmark.

Molecular Biology and Evolution
|June 23, 2001
PubMed
Summary

Molecular substitution rates vary over time, not following a strict molecular clock. New methods accurately estimate these rate changes using serially sampled molecular sequences, improving evolutionary analyses.

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Area of Science:

  • Evolutionary biology
  • Molecular evolution
  • Phylogenetics

Background:

  • Molecular sequences often exhibit rate variation, deviating from the strict molecular clock model.
  • Factors influencing substitution rates include selection pressure, population size, and generation time.

Purpose of the Study:

  • To develop and present novel methods for estimating stepwise changes in molecular substitution rates.
  • To accommodate situations where serially sampled molecular sequences are available.

Main Methods:

  • Introduction of two new methods based on multiple rates with dated tips (MRDT) models.
  • Method 1: Extension of the phylogeny-based maximum-likelihood estimation procedure.
  • Method 2: New parameterization of the pairwise distance least-squares procedure.

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Main Results:

  • The developed methods allow estimation of different substitution rates for distinct time intervals.
  • These intervals can align with sampling times or be pre-defined.
  • Demonstrated utility on a human immunodeficiency virus (HIV) sequence genealogy from a single patient.

Conclusions:

  • The new MRDT-based methods provide robust estimation of temporal variation in molecular substitution rates.
  • These advancements enhance the accuracy of evolutionary inference from serially sampled molecular data.