Viruses evolve rapidly through mutation and selection. Phylogenetics uses genetic sequences and evolutionary models to construct phylogenetic trees that trace the evolutionary relationships between organisms and can be used to date their common ancestors. Key developments in phylogenetics include faster sequencing allowing whole genome trees, improved evolutionary models accounting for different mutation types, and using Bayesian analysis via Markov chain Monte Carlo sampling to average over tree space and obtain posterior probability distributions of trees and parameters like mutation rates and dates. Software like BEAST performs Bayesian phylogenetic analysis on sequence data using strict or relaxed molecular clock models to simultaneously estimate phylogenies and dates of common ancestors.

1. Dating and tracing
the origin of viruses

2. ?
?
?
Eukaryota
Bacteria
Archaea
The most common ancestors
to all living things
We should move from gene to whole genome phylogenetic tree

3. Phylogenetics is fastly
growing field
• PCR and sequencing have boosted the science of
phylogenies
• But building phylogenies is a complex phenomenon.
• Selection of model for a set of sequences is important.

4. Evolution happens fast in
pathogens
wild type sequence
Mutation
Mutation is tolerated and
moves to next generation
Selection removes mutants

5. Different mutations different
models
• Sequence editing, alignment and models for making
phylogenetic trees
• A model can be built empirically or can be set
parametrically
• Selection of models describe the important type of
mutation.

6. Molecular clock
• In 1965, Zuckerkandl and Pauling (1965) proposed
the theory of a molecular clock, that is, that the rate
of molecular evolution is approximately constant
over time for all the proteins in all lineages.
According to this theory, any time of divergence
between genes, proteins, or lineages can be dated
simply by measuring the number of changes between
sequences. Soon afterwards, in 1969, Jukes and
Cantor (1969) proposed a stochastic model for DNA
substitution in which all nucleotide substitutions
occur at an equal rate, and when a nucleotide is
substituted, any one of the other nucleotides is
equally likely to be its replacement.

7. Markov chain Monte Carlo
• Consider a stochastic model for DNA or amino
acid sequence evolution. We assume
independence of evolution at different
sequence sites and thus can consider sites one
by one. At any single site, the model works with
probabilities Pij (T) that base i will have
changed to base j after a timeT. The subscripts
i and j take the values 1,...,4 to represent the
nucleotides A, T, C, G for DNA sequences and
1,...,20 for amino acid sequences.

8. what is BEAST? (Bayseian evolutionary
analysis for sampling tree)
• BEAST is a cross-platform program for Bayesian analysis
of molecular sequences using MCMC. It is entirely
orientated towards rooted, time-measured phylogenies
inferred using strict or relaxed molecular clock models. It
can be used as a method of reconstructing phylogenies
but is also a framework for testing evolutionary hypotheses
without conditioning on a single tree topology. BEAST
uses MCMC to average over tree space, so that each tree
is weighted proportional to its posterior probability. We
include a simple to use user-interface program for setting
up standard analyses and a suit of programs for analysing
the results.

9. How does thing work in
BEAST?
• Mutation rates
• Dating the phylogenies
• Selecting the model
• Setting the parameters based on prior information
Sequence of
influenza virus,
1918
Sequence of
influenza virus,
2009
Can I trace back
origin?