Bioinformatics

Dr. Aladdin Hamwieh Khalid Al-shamaaAbdulqader Jighly

2010-2011

Lecture 9Phylogenetic Prediction

Aleppo UniversityFaculty of technical engineeringDepartment of Biotechnology

Phylogenetic Trees and Dissimilarity estimation

3

Historical Note• Until mid 1950’s phylogenies were constructed

by experts based on their opinion (subjective criteria)

• Since then, focus on objective criteria for constructing phylogenetic trees– Thousands of articles in the last decades

• Important for many aspects of biology– Classification – Understanding biological mechanisms

Morphological vs. Molecular

• Classical phylogenetic analysis: morphological features: number of legs, lengths of legs, etc.

• Modern biological methods allow to use molecular features– Gene sequences– Protein sequences– DNA markers

5

Rat QEPGGLVVPPTDA

Rabbit QEPGGMVVPPTDA

Gorilla QEPGGLVVPPTDA

Cat REPGGLVVPPTEG

From sequences to a phylogenetic tree

There are many possible types of sequences to use (e.g. Mitochondrial vs Nuclear proteins).

.

Basic Assumptions Closer related organisms have more similar genomes.

Highly similar genes are homologous (have the same ancestor).

Phylogenetic relation can be expressed by a dendrogram (a “tree”) .

Aardvark Bison Chimp Dog Elephant

Dangers in Molecular Phylogenies

• We have to emphasize that gene/protein sequence can be homologous for several different reasons:

• Orthologs -- are genes in different species that have evolved from a common ancestral gene via speciation.

• Paralogs -- sequences diverged after a duplication event

• Xenologs -- sequences diverged after a horizontal transfer (e.g., by virus)

8

Species Phylogeny

Gene Phylogenies

Speciation events

Gene Duplication

1A 2A 3A 3B 2B 1B

Phylogenies can be constructed to describe evolution genes.

Three species termed 1,2,3.Two paralog genes A and B.

9

Types of Trees

A natural model to consider is that of rooted trees Common

Ancestor

10

Types of treesUnrooted tree represents the same phylogeny without the

root node

Depending on the model, data from current day species does not distinguish between different placements of the root.

11

Distance-Based MethodInput: distance matrix between species

For two sequences si and sj , perform a pairwise (global) alignment. Let f = the fraction of sites with different residues. Then

Outline:• Cluster species together• Initially clusters are singletons• At each iteration combine two “closest” clusters

to get a new one

3 4log(1 )4 3ijd f (Jukes-Cantor Model)

Human, Chimp, Gorilla, Orangutan, and Gibbon

UPGMA

Taxa 1 2 3 4 5 6 7OTU-1 T G C G T A TOTU-2 T G G G T A TOTU-3 T G C G C T TOTU-4 T G C T G T GOTU-5 T A G T A G C

Step 1: Generate data (Sequence/ Genotype/ Morphological) for each OTU.

Distance can be calculated by using different substitution models:1. # of nucleotide differences.2. p-distance.3. JC distance4. K2P distance.5. F816. HKY857.GTR etc

Step 2: Calculate p- distance for all pairs of taxa

Taxa 1 2 3 4 5 6 7OTU-1 T G C G T A TOTU-2 T G G G T A T

= 0.142857143

Step 3: Calculate distance matrix for all pairs of taxa and select pair of taxa with minimum distance as new OTU.

Taxa 1 2 3 4 51 0 1 2 4 62 0.1428 0 3 5 53 0.2857 0.4285 0 3 64 0.5714 0.7142 0.4285 0 55 0.8571 0.7142 0.85710.7142 0

OTU-1OTU-2

0.0714

0.0714

Step 4: Recalculate new distance matrix, assuming OTU-1 and OTU-2 as one OTU.

= 0.3571

taxa 1+2 3 4 51+2 0

3 0.35714 0 4 0.64285 0.4285 0 5 0.78571 0.8571 0.7142 0

Taxa 1 2 3 4 51 0 2 0.1428 0 3 0.2857 0.4285 0 4 0.5714 0.7142 0.4285 0 5 0.8571 0.7142 0.8571 0.7142 0

Step 5: Select pair of taxa with minimum distance as new OTU.

OTU-1

OTU-2

0.071

0.071

OTU-30.179

0.107

0.107 + 0.071 + 0.179 = 0.357

Step 6: Again select pair of OTU with minimum distance as new OTU and recalculate distance matrix.

= 0.5714

taxa (1+2)3 4 5(1+2)3 0

4 0.5714 0 5 0.8095 0.7142 0

taxa 1+2 3 4 51+2 0

3 0.35714 0 4 0.64285 0.4285 0 5 0.78571 0.8571 0.7142 0

Taxa 1 2 3 4 51 0 2 0.1428 0 3 0.2857 0.4285 0 4 0.5714 0.7142 0.4285 0 5 0.8571 0.7142 0.8571 0.7142 0

Step 7: Again select pair of taxa with minimum distance as new OTU.

OTU-2

OTU-10.071

0.071

OTU-30.179

0.107

OTU-40.286

0.107

0.107 + 0.107 + 0.071 + 0.286 = 0.571

Step 8: Again select pair of OTU with minimum distance as new OTU and recalculate distance matrix.

= 0.7857

taxa ((1+2)3)4 5

((1+2)3)4 0

5 0.7857 0

taxa (1+2)3 4 5(1+2)3 0

4 0.5714 0 5 0.8095 0.7142 0

taxa 1+2 3 4 51+2 0

3 0.35714 0 4 0.64285 0.4285 0 5 0.78571 0.8571 0.7142 0

Taxa 1 2 3 4 51 0 2 0.1428 0 3 0.2857 0.4285 0 4 0.5714 0.7142 0.4285 0 5 0.8571 0.7142 0.8571 0.7142 0

Step 9: Again select pair of OTU with minimum distance as new OTU and make final rooted tree.

OTU-2

OTU-10.071

0.071

OTU-30.179

0.107

OTU-40.286

0.107

OTU-50.393

0.107

0.393 + 0.107 + 0.107 + 0.107 + 0.071 = 0.785

Jukes-Cantor distancethe rate of nucleotide substitution is the same for all pairs of the four nucleotides A, T, C, and G A A

A CA GA TC AC CC GC TG AG CG GG TT AT CT GT T

25% similar (= distance of 0.75). 75% which is what you expect with random assignment of nucleotides to a pair of taxa

طريقة الوراثية UPGMAتفترض القرابة شجرة أفرع طول في ثابتة نسبة

=-(3/4)*LN(1-(((4/3)*0.1594)))

Neighbor-joiningطريقة • - أفرع طول في ثابتة نسبة استخدام على مارغولياش فيتش طريقة تعHتمد ال

طريقة في هي كما الوراثية القرابة UPGMAشجرةبأقل • المدروسة للوحدات أزواج أقرب تحديد على تعتمد الطريقة هذه

( . المقارب الزوج تعريف ويمكن لألفرع قيمة( Pair of neighborاألطوال بأنهجذرية ) غير بعقدة وحدتين بين (.unrooted nodeاالرتباط

والغوريال: • األنسان عكس على وحدة في متحدان والشيمبانزي اإلنسان مثال ) الغHوريال، ) مع تجاور على والشيمبانزي اإلنسان األولى الوحدة ندعو وعليه

باقي مع القرابة عن نبحث والغHوريال األولى الوحدة بين القرابة دراسة وبعد. المدروس المجتمع أفراد

• : نبدأ مدروسة أفراد ثمانية لدراسة مثالمرتبطون جميعا أنهم لو كما المقارنة

إثبات وعند بعدها واحدة، بعقدةبين على 2و 1االرتباط الشجرة تصبح

Neighbor-joiningطريقة

Neighbor-joiningطريقة

A B C D E rA (human) — 0.015 0.045 0.143 0.198 0.4010B (chimp) — 0.03 0.126 0.179 0.3500C (gorilla) — 0.092 0.179 0.3460D (orangutan) — 0.179 0.5400E (gibbon) — 0.7350

Neighbor-joiningطريقة

A B C D EA (human) — 0.0150 0.0450 0.1430 0.1980B (chimp) -0.3605 — 0.0300 0.1260 0.1790C (gorilla) -0.3285 -0.3180 — 0.0920 0.1790D (orangutan) -0.3275 -0.3190 -0.3510 — 0.1790E (gibbon) -0.3700 -0.3635 -0.3615 -0.4585 —

A:B = 0.015-(0.4010+0.35)/2

Example:

A B C D E r r/3A (human) — 0.015 0.045 0.143 0.198 0.4010 0.1337B (chimp) — 0.03 0.126 0.179 0.3500 0.1167C (gorilla) — 0.092 0.179 0.3460 0.1153D (orangutan) — 0.179 0.5400 0.1800E (gibbon) — 0.7350 0.2450

=0.179/2+(0.18-0.245)/2

=0.179-0.057

Human and chimpanzee have the smallest value of Mij and they are replaced by node 2.

dijMij

• PHYLIP (Phylogeny Inference Package)

a = 0.016

3

2

1

b = -0.001

c = 0.006

d = 0.057

e = 0.1221'= 0.0403

2'= 0.024

E

D

A

B

C• UPGMA

• Neighbor-joining (NJ)

Genetic distanceMarker1 Marker2 Marker3 Marker4 Marker5 Marker6 Marker7

Plant1 1 0 1 1 0 1 1

Plant2 1 1 1 0 0 1 0

Plant11 0

Plant2 1 Fa=3 Fb=10 Fc=2 Fd=1

N= Fa+Fb+Fc+Fd

Simple Match distance = Fa/N= 3/7= 0.43Genetic distance (Jaccard) = Fa/(Fa+Fb+Fc) = 3/6= 0.5

Dissimilarity indices – Continuous

Euclidean distance

Euclidean Distance is the most common use of distance. In most cases when people said about distance , they will refer to Euclidean distance. Euclidean distance or simply 'distance' examines the root of square differences between coordinates of a pair of objects.

Example:Point A has coordinate (0, 3, 4, 5) and point B has coordinate (7, 6, 3, -1). The Euclidean Distance between point A and B is

Features

cost time weight incentive Plant A 0 3 4 5 Plant B 7 6 3 -1

Dissimilarity indices – Continuous

Euclidean distance

Manhattan (City-Block)It is also known as Manhattan distance, boxcar distance, absolute value distance. It examines the absolute differences between coordinates of a pair of objects.

Features cost time weight incentive

Plant A 0 3 4 5 Plant B 7 6 3 -1

Thank you

PAST برنامج على تطبيق العملي جلسة