Introduction to Phylogenies

1. Introduction to Phylogenies Dr Laura Emery Laura.Emery@ebi.ac.uk www.ebi.ac.uk/training

2. Objectives After this tutorial you should be able to… • Use essential phylogenetic terminology effectively • Discuss aspects of phylogenies and their implications for phylogenetic interpretation • Apply phylogenetic principles to interpret simple trees

3. Outline • Applications of phylogenetics • What is a phylogeny or tree? • Aspects of a tree • Phylogenetic Interpretation

4. What can I do with phylogenetics? • Deduce relationships among species or genes • Deduce the origin of pathogens • Identify biological processes that affect how your sequence has evolved e.g. identify genes or residues undergoing positive selection • Explore the evolution of traits through history • Estimate the timing of major historical events • Explore the impact of geography on species diversification

5. What is a phylogenetic tree? A tree is an explanation of how sequences evolved, their genealogical relationships and thus how they came to be the way they are today (or at the time of sampling). Darwin 1837

6. Phylogenies explain genealogical relationships • Family tree

7. Aspects of a tree • Topology (branching order) • Branch lengths (indication of genetic change) • Nodes • Tips (sampled sequences known as taxa) • Internal nodes (hypothetical ancestors) • Root(oldest point on the tree) • Confidence (bootstraps/probabilities) * *

8. 1. Topology The topology describes the branching structure of the tree, which indicate patterns of relatedness. A A C B C A B B A B A B C B C C C A These trees display the sametopology These trees display differenttopologies

9. Topology Question Are these topologies the same? Answer = yes

10. Topology Question II Which of these trees has a different topology from the others? C F F F F A B E D D A A C E B D A A E B B C D C F E E C D B

11. 2. Branch lengths indicate genetic change • Longer branches indicate greater change • Change is typically represented in units of number of substitutions per site (but check the legend) 0.8 1.2 0.5 0.6 0.5 0.5

12. A scale bar can represent branch lengths These are alternative representations of the same phylogeny 0.8 1.2 0.5 0.6 0.5 0.5 0.5

13. Branch Length Question Fish Which of these statements are true? • For both gene trees, the Fish is the most genetically different of the four species compared • For both gene trees, more substitutions have occurred since the divergence of Dog and Snake than they have since Cat and Snake • Gene B has accumulated more substitutions than Gene A on the Snake lineage • Gene B has accumulated more substitutions than Gene A on the Fish lineage Dog Dog Fish Cat Cat Snake Snake 0.5 GeneA Gene B

14. Alternative representations of phylogenies All of these representations depict the same topology Branch lengths are indicated in blue Red lengths are meaningless Newick format

15. Not all trees include branch length data CladogramPhylogram

16. Distance and substitution rate are confounded • Branch lengths indicate the genetic change that has occurred • We often don’t know if long branch lengths reflect: • A rapid evolutionary rate • An ancient divergence time • A combination of both • Genetic change = Evolutionary rate x Divergence time (substitutions/site) (substitutions/site/year) (years) A B C E D

17. Alternative Representations Question

18. 3. Nodes • Nodesoccuratthe ends of branches • There are three types of nodes: • Tips (sampled sequences known as taxa) • Internal nodes (hypothetical ancestors) • Root (oldest point on the tree) A B C D E Figures Andrew Rambaut

19. The root is the oldest point on the tree present • The root indicates the direction of evolution • It is also the (hypothesised) most recent common ancestor (MRCA) of all of the samples in the tree A B C D E past Figures Andrew Rambaut

20. Trees can be drawn in an unrooted form Rooted Unrooted These are alternative representations of the same topology A B C D E A D B E C

21. There are multiple rooted tree topologies for any given unrooted tree • Most tree-building methods produce unrooted trees • Identifying the correct root is often critical for interpretation! * Figure Aiden Budd

22. How to root a tree Midpoint rooted • Midpointrooting • Assume constant evolutionary rate • Often not the case! • Outgrouprooting • The outgroup is one or more taxa that are known to have diverged prior to the group being studied • The node where the outgroup lineage joins the other taxa is the root Unrooted Outgroup rooted Recommended

23. Root Question This tree shows a cladogram i.e. the branch lengths do not indicate genetic change. Indicate any root positions where bird and crocodile are notsister taxa (each other's closest relatives).

24. 4. Confidence How good is a tree? A tree is a collection of hypotheses so we assess our confidence in each of its parts or branches independently There are three main approaches: • Bootstraps • Bayesian methods • Approximate likelihood ratio test (aLRT) methods 100 0.99 63 0.81 85 0.93 probabilistic

25. What is a monophyletic group? A monophyletic group (also described as a clade) is a group of taxa that share a more recent common ancestor with each other than to any other taxa. monophyletic group

26. Confidence Question Which of the bootstrap values indicates our confidence in the grouping of A, B, C, and D together as a monophyletic group? Do you think we can be confident in this grouping? 91 63 A B C D E F 100 84

27. Review • Topology (branching order) • Branch lengths (indication of genetic change) • Nodes • Tips (sampled sequences known as taxa) • Internal nodes (hypothetical ancestors) • Root(oldest point on the tree) • Confidence (bootstraps/probabilities) * *

28. Simple phylogenetic interpretation question • Which is true? • A) Mouse is more closely related to fish than frog is to fish • B) Lizard is more closely related to fish than mouse is to fish • C) Human and frog are equally related to fish

29. Now it is your turn… • Open your tutorial manual and begin Tree-thinking quiz 1 (appendix 1) • The manual is available to download from: http://www.ebi.ac.uk/training/course/scuola-di-bioinformatica-2013 • When you are finished you can mark your own (the answers are at the end of the quiz). • Remember to ask for help at any stage!