bcb 444/544

1BCB 444/544 F07 ISU Terribilini #29- Phylogenetics 10/31/07

BCB 444/544

Lecture 29

Phylogenetics

#29_Oct31


Mon Oct 29 - Lecture 28

Promoter & Regulatory Element Prediction

• Chp 9 - pp 113 - 126

Wed Oct 30 - Lecture 29

Phylogenetics Basics

• Chp 10 - pp 127 - 141

Thurs Oct 31 - Lab 9

Gene & Regulatory Element Prediction

Fri Oct 30 - Lecture 29

Phylogenetic Tree Construction Methods & Programs

• Chp 11 - pp 142 - 169

Required Reading (before lecture)


Assignments & Announcements

Mon Oct 29 - HW#5

HW#5 = Hands-on exercises with phylogenetics and tree-building software

Due: Mon Nov 5 (not Fri Nov 1 as previously posted)


BCB 544 "Team" Projects

Last week of classes will be devoted to Projects

• Written reports due: • Mon Dec 3 (no class that day)

• Oral presentations (20-30') will be: • Wed-Fri Dec 5,6,7

• 1 or 2 teams will present during each class period

See Guidelines for Projects posted online


BCB 544 Only: New Homework Assignment

544 Extra#2

Due: √PART 1 - ASAP

PART 2 - meeting prior to 5 PM Fri Nov 2

Part 1 - Brief outline of Project, email to Drena & Michael

after response/approval, then:

Part 2 - More detailed outline of project

Read a few papers and summarize status of problem

Schedule meeting with Drena & Michael to discuss

ideas


Seminars this Week

BCB List of URLs for Seminars related to Bioinformatics:http://www.bcb.iastate.edu/seminars/index.html

• Nov 1 Thurs - BBMB Seminar 4:10 in 1414 MBB

• Todd Yeates UCLA TBA -something cool about structure and evolution?

• Nov 2 Fri - BCB Faculty Seminar 2:10 in 102 ScI

• Bob Jernigan BBMB, ISU

•Control of Protein Motions by Structure


Chp 10 - Phylogenetics

SECTION IV MOLECULAR PHYLOGENETICS

Xiong: Chp 10 Phylogenetics Basics

• Evolution and Phylogenetics• Terminology• Gene Phylogeny vs. Species Phylogeny• Forms of Tree Representation• Why Finding a True Tree is Dificult• Procedure of Building a Phylogenetic Tree


Evolution and Phylogenetics

• Evolution – the development of biological

form from other preexisting forms

• Evolution proceeds by natural selection


Natural Selection

• Species can produce more offspring than

the environment can support. This leads

to competition for resources. Genetic

variations exist in a population that give

some individuals an advantage, others a

disadvantage, leading to differential

reproductive success.


Phylogenetics

• Phylogenetics is the study of the evolutionary history of living organisms• Uses tree like diagrams to represent the

pedigrees of the organisms

• Similarities and differences seen in a

multiple sequence alignment are easier to

make sense of in a phylogenetic tree


Data Used in Phylogenetics

• Fossil records - morphology and timeline of divergence• Limitations - not available for all species in all areas,

morphology determined by multiple genetic factors, fossils for microorganisms are especially rare

• Molecular data - DNA and protein sequences - molecular fossils• Advantages - lots of data, easy to obtain• Limitations - can be difficult to get sequences from

extinct species

• Physical, behavior, and developmental characteristics can also be used in phylogenetics


Molecular Phylogenetics

• Molecular phylogenetics is the study of evolutionary relationships of genes and other biological macromolecules by analyzing their sequences• Sequence similarity can be used to infer evolutionary relationships


Assumptions in Molecular Phylogenetics

• Sequences used are homologous, i.e. share a common ancestor• Phylogenetic divergence is bifurcating, i.e. parent branch splits into two daughter branches• Each position in a sequence evolved independently• Molecular Clock – sequences evolve at constant rates (only used in some methods)


Terminology

A B C D E F G H

Root

BranchInternal node

Taxa (terminal nodes)


Terminology

• Clade = group of taxa descended from a common ancestor• Lineage = branch path depicting ancestor-

descendant relationship• Paraphyletic group = group of taxa that share

more than one closest common ancestor

A B C D E F G H


Tree Topology

• Tree topology is the branching pattern in a tree

DichotomyBifurcation Polytomy

Multifurcation


Rooted vs. Unrooted Trees

A

DCBA

B

C

D

Rooted Tree

Unrooted Tree


Rooted vs. Unrooted Trees

• Unrooted trees have no root node – do not assume knowledge of a common ancestor, just relationships• Can convert between unrooted and rooted, but

first need to determine where the root is• Two ways to define the root:• Use an outgroup• Midpoint rooting – midpoint of the two most divergent

groups is assigned to be the root


Outgroups

• Outgroup is a sequence related to the sequences being studied, but is more distantly related• Must be distinct from the ingroup, but not too

distant• If outgroup is too distantly related, it can lead

to errors in tree construction• Trick is to find the closest related sequence

that is removed from the ingroup


Gene Phylogeny vs. Species Phylogeny

• When using molecular data, we are technically building a phylogeny for just that sequence, not for the species from which the sequences came• Species evolution is the result of mutations in

the entire genome• Your gene may have evolved differently than

other genes in the genome• To obtain a species phylogeny, we need to use

a variety of gene families to construct the tree


Forms of Tree Representation

PhylogramBranch lengths represent amount of evolutionary divergence

CladogramBranch lengths are meaningless, only topology matters


Forms of Tree Representation

• Newick format – text format for use by computer programs• Example: (((B,C),A),(D,E))• Can also have branch lengths


Consensus Trees

Multiple trees that are equally optimal – build consensus tree by collapsing disagreements into a single node


Why Finding a True Tree is Difficult

• The number of possible trees grows exponentially with the number of species (or sequences)

• Nr = (2n -3)!/2(n-2)(n-2)!

• Nu = (2n -5)!/2(n-3)(n-3)!

• To find the best tree, you must explore all possibilities (or must you?)

Number of rooted trees


Tree Building Procedure

• Choose molecular markers• Perform MSA• Choose a model of evolution•Determine tree building method• Assess tree reliability


Choice of Molecular Markers

• Very closely related organisms - nucleic acid sequence will show more differences• For individuals within a species - faster

mutation rate is in noncoding regions of mtDNA• More distantly related species - slowly

evolving nucleic acid sequences like ribosomal RNA or protein sequences• Very distantly related species - use highly

conserved protein sequences


Advantages of Protein Sequences

• More highly conserved - mutations in DNA may not change amino acid sequence

• Third position in a codon especially can vary - violates our assumption of independent evolution of all positions in a sequence

• DNA sequences can be biased by codon usage differences between species - causes variations in sequence that are not attributable to evolution

• In alignments, DNA sequences that are not related can show a lot of similarity due to only 4 letters in alphabet, proteins do not have this problem (at least not as much)

• Introducing gaps in alignments of DNA sequences can cause frameshift errors, making alignment biologically meaningless


Advantages of DNA Sequences

• Better for closely related species• Show synonymous and non-synonymous

mutations, which allows analysis of positive and negative selection events• Lots of nonsynonymous mutations may mean

positive selection for new functions of protein with different amino acid sequence• Lots of synonymous mutations may mean

negative selection - changed amino acid sequence is detrimental


Multiple Sequence Alignment

• Most critical step in tree building - cannot build correct tree without correct alignment• Should build alignments with multiple

programs, then inspect and compare to identify the most reasonable one• Most alignments need manual editing• Make sure important functional residues

align• Align secondary structure elements• Use full alignment or just parts


Automatic Editing of Alignments

• Rascal and NorMD – correct alignment errors, remove potentially unrelated or highly divergent sequences• Gblocks – detect and eliminate poorly

aligned positions and divergent regions

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