Phylogeny

1. Doug Raiford Lesson 8 Phylogeny Phylogenetics

2. Phylogeny • Definition • study of evolutionary relatedness among various groups of organisms • All life evolved from a single-celled organism • Cenancestor • Traditional techniques: • Relied upon phenotypical (observable characteristic or trait of an organism) differences Phylogenetics

3. Why important? • Understanding of the origins of life • Who we are? From whence did we come? • If can understand biological systems and how they came to be… • Perhaps can predict • Reaction to changing environments • Reaction to drugs (similar organisms will probably react similarly) • What our future holds • How we will evolve Why study phylogenetics? Phylogenetics

4. Role of bioinformatics? • DNA similar in related organisms • How would we go about measuring DNA similarity? • Must align first • Must use homologous genes/proteins • Just count the locations where different Where do genes and proteins come into the picture? Phylogenetics

5. Complicating Issues • Different rates of evolutionary change • Organisms: different environmental factors • Proteins: under different selective pressures • Regions of proteins: • Interiors, tightly packed, hydrophobic • External loops, less important forstructural integrity Phylogenetics

6. More complications: gaps • Gap of virtually any length could happen in single event Buchnera/1-356 MENL----------------DKKKALDRVIMEIEKAYGKGAIMKLG-EMA Lactobacillus/1-363 MAKD----------------EKKAALDAALKKIEKNFGKGAVMRMG-EKA Geobacter/1-338 MTQ-----------------EREKAIELALSQIEKQFGKGAIMRLGADEA Actinobacillus/1-376 MAADNKKAQKNTVTKQIDPEQKEKALAAALAQIEKQFGKGSIMRLG-DTQ Salmonella/1-353 MAID---------------ENKQKALAAALGQIEKQFGKGSIMRLG-EDR Phylogenetics

7. Complicated by HGT • DNA material doesn’t stay put • Bacteria reproduce asexually • But plasmids… • Also, viruses… • Finally, take-up… • Not surprising… • Meiosis, mitosis, translocating genes Phylogenetics

8. Reticulated form of tree • Horizontal gene transfer (HGT) • More of a bush (especially at the base) Phylogenetics

9. Solutions: picking the right gene • Need a gene that is in all organisms (ubiquitous) • The gene should be evolutionarily stable (very similar in all organisms) • Should compare regions of the gene that are highly conserved Phylogenetics

10. Mitochondrial DNA • Circular DNA found in organelles outside the nucleus • No crossover: passed down in the egg • Exact copy from female parent • Mitochondria are the powerhouse of the cell • Break-down food, release energy Phylogenetics

11. Ribosomal RNA (16S) • Dominant molecule in microbial ribosomes (translation) • Ubiquitous, same role in every organism • Highly conserved Phylogenetics

12. How find conserved regions? • Multiple sequence alignments • ClustalW • Easily identify regions that are highly conserved Sound familiar? What tools do we already have? atgccgca-actgccgcaggagatcaggactttcatgaatatcatcatgcgtggga-ttcag acctccatacgtgccccaggagatctggactttcacc---tggatcatgcgaccgtacctac t-atgg-t-cgtgccgcaggagatcaggactttca-gt--g-aatcatctgg-cgc--c-aa t--tcgt-ac-tgccccaggagatctggactttcaaa---ca-atcatgcgcc-g-tc-tat aattccgtacgtgccgcaggagatcaggactttcag-t--a-tatcatctgtc-ggc--tag Phylogenetics

13. Woeseet al. 1977 • Used 16S to investigate tree of life • Discovered three domains (not two) Phylogenetics

14. Goal • Build cladogram or phylogram: • A tree diagram used to illustrate phylogenetic relationships • Length of each branch = number of sequence changes that occurred (except in cladogram where length not used) • The amount of time usually not known Sometimes utilize a dendrogram Phylogenetics

15. Trees • Each sequence taxon (plural: taxa) • Each subtree = clade (long “a”) • Tree length • Sum of all the branch lengths Sometimes utilize a dendrogram Phylogenetics

16. Molecular clock hypothesis • Assumption of a uniform rate of mutation in the tree branches • Is this reasonable? • Allows some conclusions to be drawn Phylogenetics

17. Three methods • Distance • Maximum parsimony • Maximum likelihood • Main packages • PAUP • PHYLIP Phylogenetics

18. Distance methods • Unweighted pair group method with arithmetic mean (UPGMA) • One of the first and simplest distance methods • Basically hierarchical clustering Phylogenetics

19. Distance • Need all pair-wise distances • How measure distance? • Want to measure the number of mutations that occurred since the species split Count up the number of columns where there are differences and divide by the length of the sequences: the probability of a mutation at a given location Distance between organism A and B is 4 2 2 Organism A Organism B Phylogenetics

20. All pair-wise distances Example: distance matrix 1 1 3 1 2 1 A B C D Phylogenetics

21. Algorithm for building tree • Find closest • Place next to each other in tree • Find average distanceto rest 1 1 3 1 2 1 A B C D Phylogenetics

22. Algorithm for building tree • Find the next closest • Place next to each other in tree 1 1 3 1 2 1 A B C D Phylogenetics

23. New distance matrix Now for a tougher example A B C D Phylogenetics

24. Algorithm for building tree • C and D still closest • So start tree with these two • Find average distanceto rest A B C D Phylogenetics

25. Tree representation • (A,(B,(C,D))) • ((A,B),(C,D)) • Binary trees A C D B A B C D Phylogenetics

26. Algorithm for building tree • Find the next closest • Place next to each other in tree (collapse B with CD) A B C D Phylogenetics

27. Phylogenetics