Phylodynamics and the coalescent
Lecturer: Alexei Drummond

Virus Phylodynamics

"Skyline" coalescent model

The generalized skyline plot

Introduced by Pybus and Strimmer (2001).

  • Visual framework for exploring the demographic history of sampled DNA sequences
  • Input: a single estimated ancestral genealogy (a tree)
  • Output: nonparametric plot of the population size through time
  • Groups adjacent coalescent intervals
  • Converts information within these intervals to estimates of population size

for a single coalescent interval:

\[\hat{N}_k = \binom{k}{2}t_k\]

for \(j\) adjacent intervals:

\[\hat{N}_{k,j} = \frac{k(k-j)}{2j}\sum_{i=k-j+1}^k{t_i}\]

The generalized skyline plot - simulated data

Constant population size, \(N(t)=N_0\)
Exponential growth, \(N(t) = N_0 e^{-rt}\)

The generalized skyline plot - HIV-1 group M

The tree used here was estimated in Yusim et al (2001) Phil. Trans. Roy. Soc. Lond. B 356:855-866.

The black curve is a parametric coalescent estimate obtained from the same data under the expansion model, \(N(t) = (N_0-N_A)e^{-rt}+N_A\)

The Bayesian skyline plot

The Bayesian skyline plot (Drummond et al, 2005) estimates a demographic function that has a certain fixed number of steps (in this example 15) and then integrates over all possible positions of the break points, and population sizes within each epoch.

Detecting evolutionary bottlenecks using BSP

480 contemporaneous samples from a single locus

Detecting evolutionary bottlenecks using BSP

16 contemporaneous samples from each of 32 loci

Detecting evolutionary bottlenecks using BSP

480 samples sampled through time from a single locus

The population dynamics of genetic diversity in Influenza A

Rambaut et al (2008) Nature 453:615-620

Validating the Bayesian skyline plot

BSP versus parametric coalescent model

Hepatitis C in Egypt

Modeling complex demographic history

Dengue 4 in Puerto Rico

  • N(t) = N0exp(-rt)
    • log marginal likelihood = -10566.421
  • N(t) = scaled-translated case data
    • log marginal likelihood = -10478.572

Comparing BSP to incidence data

Dengue 4 in Puerto Rico