Multiple Sequence Alignment. Sequences

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1 Multiple Sequence Alignment Sequences > YOR020c mstllksaksivplmdrvlvqrikaqaktasglylpe knveklnqaevvavgpgftdangnkvvpqvkvgdqvl ipqfggstiklgnddevilfrdaeilakiakd > crassa mattvrsvksliplldrvlvqrvkaeaktasgiflpe ssvkdlneakvlavgpgaldkdgkrlpmgvnagdrvl ipqyggspvkvgeeeytlfrdseilakiae > nidulans msllrnvknlaplldrvlvqrvkpeaktasgiflpes svkeqneakvlavgpgavdrngqripmgvaagdrvlv pqfggsplkigeeeyhlfrdseilakine > pombe (fission yeast) matklksaksivplldrilvqrikadtktasgiflpe ksveklsegrvisvgkggynkegklaqpsvavgdrvl lpayggsnikvgeeeyslyrdhellaiike > alpina masritkfsktivpmmdrvlvqrikpqqktasgiyip ekaqealnegyvvavgkglttqegkvvpselaegdkv llppyggsvvkvdneelilfreseilakiq > cohnii matgiakrftplldrvlvqrlkpeaktasglflpesa akapnyatvlavgpggrtrdgdilpmnvkvgdkvvvp eyggmtlkfedeefqvfrdadimgilne > melanogaster maaaikkiipmldriliqraealtktkggivlpekav gkvlegtvlavgpgtrnastgnhipigvkegdrvllp efggtkvnlegdqkelflfresdilakle > sapiens agqafrkflplfdrvlversaaetvtkggimlpeksq gkvlqatvvavgsgskgkggeiqpvsvkvgdkvllpe yggtkvvlddkdyflfrdgxilgky > stearothermophilus vlkplgdrvvievieteektasgivlpdtakekpqeg rvvavgkgrvldsgervapevevgdriifskyagtev kydgkeylilresdilavig > tuberculosis makvnikpledkilvqaneaetttasglvipdtakek pqegtvvavgpgrwdedgekripldvaegdtviysky ggteikyngeeylilsardvlavvsk > musculus (house mouse) magqafrkflllfdrvlversaaetvtkggimlpeks qgkvlqatvvavgsggkgksgeiepvsvkvgdkvllp eyggtkvvlddkdyflfrdsdilgkyvn 1

2 Multiple Sequence Alignment (MSA) Why MSA? Proteins are often related to a larger group (i.e., a family) of proteins Multiple sequence alignment is more sensitive than pairwise alignment for detecting homologs MSAs can elucidate conserved residues, motifs, or other functional regions in a protein MSA is critical for phylogenetic analysis Selection of sequences Multiple sequence alignment of sequences Tree building Tree evaluation 2

3 Pairwise Alignment 3-sequence Alignment AGA AGT TCC A G A T C C A G T

4 Sequences > YOR020c mstllksaksivplmdrvlvqrikaqaktasglylpe knveklnqaevvavgpgftdangnkvvpqvkvgdqvl ipqfggstiklgnddevilfrdaeilakiakd > crassa mattvrsvksliplldrvlvqrvkaeaktasgiflpe ssvkdlneakvlavgpgaldkdgkrlpmgvnagdrvl ipqyggspvkvgeeeytlfrdseilakiae > nidulans msllrnvknlaplldrvlvqrvkpeaktasgiflpes svkeqneakvlavgpgavdrngqripmgvaagdrvlv pqfggsplkigeeeyhlfrdseilakine > pombe (fission yeast) matklksaksivplldrilvqrikadtktasgiflpe ksveklsegrvisvgkggynkegklaqpsvavgdrvl lpayggsnikvgeeeyslyrdhellaiike > alpina masritkfsktivpmmdrvlvqrikpqqktasgiyip ekaqealnegyvvavgkglttqegkvvpselaegdkv llppyggsvvkvdneelilfreseilakiq > cohnii matgiakrftplldrvlvqrlkpeaktasglflpesa akapnyatvlavgpggrtrdgdilpmnvkvgdkvvvp eyggmtlkfedeefqvfrdadimgilne > melanogaster maaaikkiipmldriliqraealtktkggivlpekav gkvlegtvlavgpgtrnastgnhipigvkegdrvllp efggtkvnlegdqkelflfresdilakle > sapiens agqafrkflplfdrvlversaaetvtkggimlpeksq gkvlqatvvavgsgskgkggeiqpvsvkvgdkvllpe yggtkvvlddkdyflfrdgxilgky > stearothermophilus vlkplgdrvvievieteektasgivlpdtakekpqeg rvvavgkgrvldsgervapevevgdriifskyagtev kydgkeylilresdilavig > tuberculosis makvnikpledkilvqaneaetttasglvipdtakek pqegtvvavgpgrwdedgekripldvaegdtviysky ggteikyngeeylilsardvlavvsk > musculus (house mouse) magqafrkflllfdrvlversaaetvtkggimlpeks qgkvlqatvvavgsggkgksgeiepvsvkvgdkvllp eyggtkvvlddkdyflfrdsdilgkyvn Multiple Sequence Alignment 4

5 Pairwise Alignment Scores Schizoscchrmycs Guide Tree 5

6 Constructing a Guide Tree Unweighted pair group method with arithmetic mean (UPGMA) Neighbor joining (NJ) Unweighted Pair Group Method with Arithmetic mean (UPGMA) Assume each organism is its own group Repeat the following step Merge together the two closest groups 6

7 Unweighted Pair Group Method with Arithmetic mean (UPGMA) Unweighted Pair Group Method with Arithmetic mean (UPGMA) 7

8 Unweighted Pair Group Method with Arithmetic mean (UPGMA) Unweighted Pair Group Method with Arithmetic mean (UPGMA) 8

9 Unweighted Pair Group Method with Arithmetic mean (UPGMA) Unweighted Pair Group Method with Arithmetic mean (UPGMA) 9

10 Unweighted Pair Group Method with Arithmetic mean (UPGMA) Unweighted Pair Group Method with Arithmetic mean (UPGMA) 10

11 Unweighted Pair Group Method with Arithmetic mean (UPGMA) Unweighted Pair Group Method with Arithmetic mean (UPGMA) 11

12 Unweighted Pair Group Method with Arithmetic mean (UPGMA) Guide Tree 12

13 Neighbor Joining (NJ) Generate full tree with starlike structure Repeat the following step Connect two closest groups (i.e., neighbors) through a single node Neighbor Joining 13

14 Neighbor Joining Neighbor Joining 14

15 Neighbor Joining Neighbor Joining 15

16 Neighbor Joining Neighbor Joining 16

17 Neighbor Joining Neighbor Joining 17

18 Neighbor Joining Multiple Sequence Alignment 18

19 Multiple Sequence Alignment Multiple Sequence Alignment 19

20 What can phylogeny do for you? Why do we care about evolution and the evolutionary history of organisms? OR How do we benefit from phylogeny? AND How is bioinformatics related to any of this? What are the goals of phylogeny? All life forms share a common origin and are part of the Tree of Life 1) Deduce correct trees of life for all species 2) Infer or estimate divergence times How can we use phylogenetic analyses? 20

21 Revolutionalizing the Tree of Life Carl Woese: rrna IDs Archaea as separate branch of Tree of Life Discovering new life forms 21

22 Developing effective snakebite antivenins Identifying emergent diseases 22

Protecting ecosystems from invasive species Eurasian water

tree terminology Branches or Lineages A B Terminal Nodes

Tree Internal Nodes hypothetical taxanomic units (HTUs) C D E

23 Protecting ecosystems from invasive species Eurasian water milfoil Purple loosetrife Caulerpa taxifolia Common phylogenetic tree terminology Branches or Lineages A B Terminal Nodes operational taxanomic units (OTUs) Ancestral Node or ROOT of the Tree Internal Nodes hypothetical taxanomic units (HTUs) C D E Represent the TAXA (genes, populations, species, etc.) used to infer the phylogeny 23

24 Phylogenetic trees can be drawn many ways Clade: group with a single common ancestor and its descendents A B C D E A-B-C clade B-C clade D-E clade 24

25 Phylogenetic trees can be rooted or unrooted A B B C Rooted C D D Unrooted A Specifies evolutionary path Root node is most recent common ancestor of all TUs; specifies time flow Shows degree of kinship Doesn t make assumptions or require knowledge of common ancestor Phylogenetic trees can be scaled or unscaled C B C B D A D A Unscaled Branch length not proportional to number of changes/distance Scaled Branch length proportional to number of changes/distance Cladogram Phylogram 25

26 Phylogenetic trees diagram evolutionary relationships B C A D No meaning to the spacing between the taxa, or to the order in which they appear from top to bottom. E 1) No scale (cladograms) 2) Proportional to genetic distance (phylograms) 3) Proportional to time (ultrametric trees) Rotating clades: same meanings B C A D E A B C = E D 26

27 Interpreting phylogenetic trees Is the frog more closely related to the fish or the human? How are phylogenetic trees built? Traditionally: use homologous structures Caveats: - Closely related organisms don t always look similar - Similar looking organisms not always closely related - How do you decide importance of traits? 27

28 Structural analogy can result from convergent evolution Classification based on traits can be tricky cell number organelles 28

29 Molecular phylogenetic trees Large molecular data sets: Bioinformatics! Molecular clock vs. punctuated equilibrium Eliminates analogy and trait selection issues Result: great improvement on classical phylogenies Caveat: Gene divergence may not correlate with species divergence Molecular phylogenies can be constructed using different elements Nuclear genes Mitochondrial DNA Genome structure Reasonably well conserved, present in common ancestors Usually integrate analyses of multiple different genes 29

30 Molecular comparisons vs. body plans = = Which species are the closest living relatives of modern humans? Gorillas Chimpanzees Bonobos Orangutans Humans Humans Chimpanzees Bonobos Gorillas Orangutans MYA 0 14 MYA 0 Pre-molecular view Great apes (chimpanzees, gorillas and orangutans) formed a clade separate from humans. MitoDNA, most nuclear genes, and DNA hybridization Bonobos and chimpanzees are related more closely to humans than either are to gorillas. 30

31 What is the closest living relative of whales? Phylogenetic trees are hypotheses How do you construct phylogenetic trees? What computational strategies are used? How do you test the robustness of hypotheses? 31

Algorithms in Bioinformatics

Algorithms in Bioinformatics Sami Khuri Department of Computer Science San José State University San José, California, USA khuri@cs.sjsu.edu www.cs.sjsu.edu/faculty/khuri Distance Methods Character Methods