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## PowerPoint Slideshow about 'Phylogenetic Inference' - Gabriel

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Presentation Transcript

Our Goals

- Infer Phylogeny
- Optimality criteria
- Algorithm
- Phylogenetic inference
- (interesting ones)

Chuck Staben

Watch Out

“The danger of generating incorrect results is inherently greater in computational phylogenetics than in many other fields of science.”

“…the limiting factor in phylogenetic analysis is not so much in the facility of software applicaition as in the conceptual understanding of what the software is doing with the data.”

Chuck Staben

Phylogenetic Models

- No transfer of genetic information by hybridization
- All sequences are homologous
- Each position in alignment homologous
- Observed variation is valid sample from included group
- Positions evolve independently

Chuck Staben

Steps in Analysis

- Data Model (Alignment)
- alignment method
- “trimming” to a phylogenetic set
- DNA base substitution model
- Build Trees
- Algorithm based vs Criterion based
- Distance based vs Character-based

Chuck Staben

Choice of Input Data

- Data Type
- Aligned sequences, RFLP, morphological data…
- Molecule of interest
- rRNA (general purpose)
- interesting character
- Number/type of taxa
- ingroup and outgroup

Informative

Chuck Staben

rRNA Genes

- Conserved across kingdoms
- Varies within species
- Widely sequenced, easy
- Long, lots of characters

Duplication?

Chuck Staben

Multiple Alignment Method

- Computer dependence
- Phylogenetic Assumptions
- Alignment parameters
- (substitution matrix, gap cost)
- Aligned features
- primary sequence, structure
- Optimization
- statistical, non-statistical

Chuck Staben

Typical Alignment Method

- CLUSTAL, then manual editing
- Manual editing for phylogeny
- phylogenetic assumption in guide tree
- parameters a priori and dynamic
- primary structure (with some “influence”
- optimization non-statistical

Chuck Staben

Substitution Models

- G to A, C to T versus N to N
- amino acid substitution
- forwards and backwards identical?
- site-to-site variation

Simpler model better

Estimate from "quick" tree building,

Observed Variation

Chuck Staben

Tree-Building Methods

- Distance
- UPGMA, NJ, FM, ME
- Character
- Maximum Parsimony (PAUP)
- Maximum Likelihood (PHYLIP)

Acrimonious Debates

Chuck Staben

Distance Methods

- Measure distance (dissimilarity)
- Accurate if distances are all summative (ultrametric)
- NEVER true over large distance
- Methods
- UPGMA (Unweighted pair group method with Arithmetic Mean)
- NJ (Neighbor joining)
- FM (Fitch-Margoliash)
- ME (Minimal Evolution)

Most Often Wrong!

CLUSTAL

Chuck Staben

Which Distance Method?

- UPGMA
- Least accurate, most used
- NJ
- EXTREMELY RAPID
- GIVES ONLY 1 TREE
- ME and FM seem best
- Minimize tree path lengths

Chuck Staben

Character Methods

- Maximum Parsimony
- minimal changes to produce data
- can use different substitution models
- Maximum Likelihood
- turns problem “inside out”
- coin flip analogy
- increasingly popular

Chuck Staben

Searching for Trees

Chuck Staben

Tree Search Algorithms

- Exhaustive
- VERY INTENSIVE
- Branch and Bound
- Compromise
- Heuristic
- FAST (usually start with NJ)

Chuck Staben

Evaluating Trees

- Consenus Tree
- Randomized Trees
- Skewness tests
- Randomized Character Data
- Permutation tests
- Bootstrap, Jackknife
- resampling techniques
- >70% probably correct; 50% overestimates accuracy

Chuck Staben

Rooting Trees

- Molecular Clock
- Root=midpoint, longest span
- Almost ALWAYS WRONG
- Extrinsic Evidence
- select fungus as root for plants, eg
- long branch attraction can be problem
- Paralog rooting
- long branch problems

Chuck Staben

Tree Congruence

- Tree-to-Tree Comparison
- 2 different characters/same groups
- Important for evaluating biological hypotheses
- lentiviruses diverged within their current hosts only
- plant pathogenicity has arisen many times in fungi

Chuck Staben

Common Software

- PAUP
- GCG
- Pileup, Lineup, Paupsearch, Paupdisplay
- PAUPSTAR (MACs best!)
- PHYLIP
- UNIX (Seqanal)

Chuck Staben

Phylogenetic Stories

- HIV
- complete genome accessible
- evolution rapid
- selection, neutralism?
- human interest (dentist and his patients, eg.)
- Coevolution, host and pathogen
- Big Tree

Chuck Staben

Phylogenetic Resources

- NCBI Taxonomy Browser
- http://www.ncbi.nlm.nih.gov/Taxonomy/
- RDP database
- http://rdpwww.life.uiuc.edu/
- “Tree of Life”
- http://phylogeny.arizona.edu/tree/phylogeny.html

Chuck Staben

Practicalities

- Quality of input data critical
- Examine data from all possible angles
- distance, parsimony, likelihood
- Outgroup taxon critical
- problem if outgroup shares a selective property with a subset of ingroup
- Order of input can be problematic
- Jumble them!

Chuck Staben

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