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BCB 444/544. Lecture 29 Phylogenetics #29_Oct31. Required Reading ( before lecture). 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

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bcb 444 544
BCB 444/544

Lecture 29

Phylogenetics

#29_Oct31

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

required reading before lecture
Required Reading (before lecture)

MonOct 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

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

assignments announcements
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 444/544 F07 ISU Terribilini #29- Phylogenetics

bcb 544 team projects
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 444/544 F07 ISU Terribilini #29- Phylogenetics

bcb 544 only new homework assignment
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

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

seminars this week
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 YeatesUCLATBA -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

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

chp 10 phylogenetics
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

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

evolution and phylogenetics
Evolution and Phylogenetics
  • Evolution – the development of biological form from other preexisting forms
  • Evolution proceeds by natural selection

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

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.

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

phylogenetics
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

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

data used in phylogenetics
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

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

molecular 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

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

assumptions in molecular phylogenetics
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)

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

terminology
Terminology

A

B

C

D

E

F

G

H

Taxa (terminal nodes)

Internal node

Branch

Root

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

terminology1
Terminology

A

B

C

D

E

F

G

H

  • 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

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

tree topology
Tree Topology
  • Tree topology is the branching pattern in a tree

Dichotomy

Bifurcation

Polytomy

Multifurcation

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

rooted vs unrooted trees
Rooted vs. Unrooted Trees

Rooted Tree

C

A

B

D

Unrooted Tree

C

A

B

D

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

rooted vs unrooted trees1
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

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

outgroups
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

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

gene phylogeny vs species phylogeny
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

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

forms of tree representation
Forms of Tree Representation

Phylogram

Branch lengths represent amount of evolutionary divergence

Cladogram

Branch lengths are meaningless, only topology matters

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

forms of tree representation1
Forms of Tree Representation
  • Newick format – text format for use by computer programs
  • Example: (((B,C),A),(D,E))
  • Can also have branch lengths

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

consensus trees
Consensus Trees

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

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

why finding a true tree is difficult
Why Finding a True Tree is Difficult

Number of rooted trees

  • 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?)

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

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

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

choice of molecular markers
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

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

advantages of 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

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

advantages of dna sequences
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

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

multiple sequence alignment
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

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

automatic editing of alignments
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

BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

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