Lecture 7

Question 1

1. What is Phylogenetics?

Answer 1

• Phylogenetics is the study of the evolutionary history of living organisms using tree-like diagrams to represent pedigrees of these organisms.

Question 2

2. what is phylogeny?

Answer 2

• The tree branching patterns representing the evolutionary divergence are referred to as phylogeny.

Question 3

3. How do we study phylogenetics?

Answer 3

• Fossil records
• Molecular fossils

Question 4

4. What are the different applications of phylogeny

Answer 4

• Tree of life: Analyzing changes that have occurred in evolution of different organisms
• Phylogenetic relationships among genes can help predict which ones might have similar functions (e.g., ortholog detection) or also paralog
• Follow changes occurring in rapidly changing species (e.g., influenza virus)

Question 5

5. How can we detect ortholog?

Answer 5

• If we get a sequence and we know to know the fuction then we would align the sequence to see their similarity
• Ortholog first step is to align sequences and dectect their similarities

Question 6

7. What are the major assumptions in phylogenetics?

Answer 6

• The molecular sequences used in phylogenetic construction are homologous —- they share a common origin and subsequently diverged through time.
• Phylogenetic divergence is assumed to be bifurcating — a parent branch splits into 2 daughter branches at any given point.
• Each position in a sequence evolved independently.

Question 7

Explain each part of the phylogeny tree

1. taxa
2. Branches
3. Root
4. Internal node

Answer 7

Question 8

What is the difference between dichotomy and polytomy and show in the picture

Answer 8

• Dichotomy: branches bifurcate on a tree à each ancestor divides and gives rise to 2 descendants.
• Polytomy: a branch point have more than 2 descendants, resulting in a multifurcating node

Question 9

What is the difference between internal nodes and external nodes

Answer 9

• External nodes: things under comparison; operational taxonomic units (OTUs)
• Internal nodes: ancestral units; hypothetical; goal is to group current day units

Question 10

What is tree topology

Answer 10

The banching pattern in a tree

Question 11

What are the different branching patterns seen in a tree?

Answer 11

Dichotomy

Polytomy

Unrooted phylogenetic

Rooted phylogenetic

Question 12

Explain the difference between unrooted and rooted phylogenetic tree

Answer 12

• Unrooted phylogenetic tree:

does not assume knowledge of a common ancestor, but only positions the taxa to show their relative relationships.

• Rooted tree:

all sequences under study have a common ancestor or root node from which a unique evolutionary path leads to all other nodes à molecular clock hypothesis

Question 13

What are the different forms of tree presentation?

Answer 13

1. Phylogram
2. Cladogram

Question 14

Explain the difference between phylogram and cladogram and their advantages

Answer 14

• Phylogram: the branch lengths represent the amount of evolutionary divergence. (scaled tree)
• Adv: showing both the evolutionary relationships and information about the relative divergence time of the branches.
• Cladogram: the external taxa line up neatly in a row or column. (unscaled tree)
• No phylogenetic meaning, only the topology of the tree matters à shows the relative ordering of the taxa.

Question 15

What are some of the different types of phylogeny packages?

Answer 15

1. MEGA - molecular Evolutionary genetics analysis
2. POWER
3. PHYLIP

Question 16

11. What data is used to build trees?

Answer 16

• Traditionally: morphological features (e.g., number of legs, beak shape, etc.)
• Today: Mostly molecular data (e.g., DNA and protein sequences) à Molecular phylogenetics

Question 17

12. What are the two categories the data for phylogeny is classified into

Answer 17

• Can be classified into two categories:

• Numerical data
• Distance between objects
o e.g., distance (man, mouse)= 500,
o distance (man, chimp)= 100
o Usually derived from sequence data

• Discrete characters
• Each character has finite number of states
o e.g., number of legs = 1, 2, 4
o e.g., DNA = {A, C, T, G}

Question 18

13. What are the three methods used to reconstruct trees

Answer 18

• Distance methods: evolutionary distances are computed for all OTUs and build tree where distance between OTUs “matches” these distances
• Maximum parsimony (MP): choose tree that minimizes number of changes required to explain data
• Maximum likelihood (ML): under a model of sequence evolution, find the tree which gives the highest likelihood of the observed data

Question 19

Explain Taxa

Answer 19

current day species or sequences at the tips of the branches

Question 20

Explain node

Answer 20

the connecting point where 2 adjacent branches join  represents an inferred ancestor of extant taxa.

Question 21

Explain clade

Answer 21

Monophyletic group

A group of taxa descended from a single common ancestor

Question 22

Explain lineage

Answer 22

The branch path depicting an ancestor-descendant relationship on a tree

Question 23

Explain paraphyletic

Answer 23

A number of taxa share more than one closet common anestor

Question 24

Explain molecular clock

Answer 24

an assumption by which molecular sequences evolve at constant rates so that the amount of accumulated mutations is proportional to evolutionary time. (unify the evolutionary rates)

Question 25

What are some programs that are used for phylogenetic relationships among organisms?

Answer 25

1. Entrez 2. Ribosomal database project 3. Tree of life

Question 26

How to find the number of possible unrooted trees?

Answer 26

Given n OTUs, there are (2n-5) / (2^n-3 (n-3) ) unrooted trees

Question 27

What is the number of possible rooted trees?

Answer 27

Given n OTUs, there are (2n-3) / (2^n-2 (n-2) ) rooted trees

Question 28

Explain Parsimony.

Answer 28

* Find tree which minimizes number of changes needed to explain data * tree includes hypothesis of sequence at each of the nodes

Question 29

What is the problem with parsimony? Parsimony weakness?

Answer 29

Parsimony analysis implicity assumes that rate of change along branches are similar

Question 30

What the three different distance methods?

Answer 30

* Calculate pairwise distances (different distance measures, correction for multiple hits, correction for codon bias) * Make distance matrix (table of pairwise corrected distances) * Calculate tree from distance matrix

Question 31

How to calculate tree from a distance matrix?

Answer 31

Calculate tree from distance matrix: * using optimality criterion (e.g.: smallest error between distance matrix and distances in tree such as Cavalli-Sforza criterion or Fitch-Margoliash criterion: minimize), or * Algorithm approaches (UPGMA or neighbor joining) Unfortunately, both lead to computationally intractable problems (e.g., enumerating)

Question 32

Explain the distance method Heuristic UPGMA

Answer 32

* UPGMA (Unweighted Pair Group Method with Arithmetic mean) * Sequential clustering algorithm * Start with things most similar * Build a composite OTU * Distances to this OTU are computed as arithmetic means * From new group of OTUs, pick pair with highest similarity etc. * Average-linkage clustering

Question 33

What are the weaknesses of UPGMA?

Answer 33

UPGMA assumes that the rates of evolution are the same among different lineages In general, this method should not be used for phylogenetic tree reconstruction (unless we can make the assumption) Produces a rooted tree

Question 34

Explain the distance method: neighbor joining

Answer 34

Most widely-used distance based method for phylogenetic reconstruction UPGMA illustrated that it is not enough to just pick closest neighbors Key concept: consider averaged distances to other leaves as well Produces an unrooted tree

Question 35

Explain maximum likelihood

Answer 35

Maximum likelihood (ML) evaluates the probability that the chosen evolutionary model will have generated the observed sequences. The idea is that a history with a higher probability of reaching the observed state is preferred to a history with a lower probability

Question 36

What are the pros and cons of maximum likelihood?

Answer 36

Pro: * have often lower variance than other methods * workable even with very short sequences * different tree topologies evaluation * use all the sequence information Con: * very CPU intensive ---- extremely slow * the result is dependent on the model of evolution used

Question 37

Explain the phylogeny flowchart

Answer 37

Question 38

What is used for assessing reliability?

Answer 38

Bootstrap method

Question 39

What are the differences in methods

Answer 39

Maximum-likelihood (ML) and parsimony methods have models of evolution Distance methods * frequently used as the basis for progressive and iterative types of MSA * Con: inability to efficiently use information about local high-variation regions that appear across multiple subtrees Religious wars over which methods to use: * Most people now believe ML based methods are best: * most sensitive at large evolutionary distances; BUT also most time-consuming & depend on specific model of evolution used * Most commonly used packages contain software for all three methods: may want to use more than 1 to have confidence in built tree

Question 40

What program to use for parsimony?

Answer 40

DNApenny Protpars

Question 41

What program to use for distance?

Answer 41

Compute distance measure using DNAdist

Question 42

What program to use for Neighbor?

Answer 42

Protdist Neighbor joining NJ UPGMA

Question 43

What program to use for Maximum Likelihood?

Answer 43

DNAml

Question 44

What are the steps for Neighbor joining NJ algorithm?

Question 45

Explain nj performance?

Answer 45

Works well in practice If there is a tree that fits the matrix, it will find it Can sometimes get trees with negative length edges (!)

Question 46

Explain computing distances between sequences - Jukes and cantor model

Answer 46

Jukes & Cantor model: * Each position in DNA sequence is independent * Each position can mutates with same probability to any other base Correction to observed substitution rate (see notes):

Question 47

What are the 2 independent assumptions made by maximum likelihood

Answer 47

Makes 2 independence assumptions Different sites evolve independently Diverged sequences (or species) evolve independently after diverging

Question 48

What are the two computational problems with parsimony?

Answer 48

Two computational problems * (Easy) Given a particular tree, how do you find minimum number of changes need to explain data? (Fitch) * (Hard) How do you search through all trees?

Question 49

Explain the idea of parsimony: fitch's algorithm

Answer 49

Idea: construct set of possible nucleotides for internal nodes, based on possible assignments of children