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BCB 444/544

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

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  1. BCB 444/544 Lecture 29 Phylogenetics #29_Oct31 BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. Terminology A B C D E F G H Taxa (terminal nodes) Internal node Branch Root BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

  15. 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

  16. Tree Topology • Tree topology is the branching pattern in a tree Dichotomy Bifurcation Polytomy Multifurcation BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

  17. Rooted vs. Unrooted Trees Rooted Tree C A B D Unrooted Tree C A B D BCB 444/544 F07 ISU Terribilini #29- Phylogenetics

  18. 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

  19. 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

  20. 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

  21. 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

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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

  28. 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

  29. 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

  30. 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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