Estimating mutation rate and generation time from longitudinal samples of DNA sequences

Area of Science:

• Population Genetics
• Virology
• Molecular Evolution

Background:

• Estimating mutation rates and generation times is crucial for understanding viral evolution.
• Previous methods may be limited by assumptions about population structure and size.
• Longitudinal sampling offers a unique opportunity to track genetic changes over time.

Purpose of the Study:

• To develop a simple, unbiased method for estimating mutation rate per site per year.
• To simultaneously estimate the length of a generation when the mutation rate per site per generation is known.
• To apply this method to human immunodeficiency virus type 1 (HIV-1) sequence data.

Main Methods:

• Utilizing DNA polymorphisms within longitudinal samples.
• Developing an estimator unbiased under various population models (e.g., population structure, variable population size).
• Applying the estimator to env gene sequences of HIV-1 from a single patient.

Main Results:

• The mutation rate per site per year for HIV-1 was estimated at 1.62 x 10(-2).
• The length of an HIV-1 generation was estimated at 1.8 days, aligning with viral load data.
• The study identified potential reasons for discrepancies with previous generation time estimates.

Conclusions:

• The presented method provides a robust way to estimate mutation rates and generation times.
• The estimated HIV-1 generation length supports existing data but differs from some prior estimates.
• Further investigation into estimator differences is warranted for a comprehensive understanding of viral evolution.