The Cobweb of Life Revealed by Genome-Scale Estimates of Horizontal Gene Transfer

1. The Cobweb of Life Revealed by Genome-Scale Estimates of Horizontal Gene Transfer By Fan Ge, Li-San Wang,JunhyongKim Published: August 30, 2005 Presented By: Vishal S. Doshi Course: CS 502 15th April 2014

2. Fact of the day "Biology is the only science in which multiplication means the same thing as division."

3. Agenda • Terminologies • Motivation • Overview • Experiment • Conclusion

4. Terminologies • Phylogeny: History of the  Evolution of a species or group, especially lines of descent and relationships among broad groups.

5. Terminologies Tree of Life

6. Terminologies • Horizontal Gene Transfer (HGT): Horizontal gene transfer occurs when genes jump between unrelated organisms.

7. Terminologies • Horizontal Gene Transfer (HGT): Horizontal gene transfer occurs when genes jump between unrelated organisms. E.g. Think of it as acquiring genes from your neighbor instead of your parents. 

8. Terminologies Horizontal Gene Transfer (HGT)

9. Pun Intended Why is the mushroom always asked to a party?

10. Pun Intended Why is the mushroom always asked to a party? Because he’s a fungi (fun guy).

11. Agenda • Terminologies • Motivation • Overview • Experiment • Conclusion

12. Motivation There are 10 types of people in the world:

13. Motivation There are 10 types of people in the world: 01. Those who understand binary, and

14. Motivation There are 10 types of people in the world: 01. Those who understand binary, and 10. those who don't.

15. Motivation Similarly, there are 2 types of people in the world:

16. Motivation Similarly, there are 2 types of people in the world: • Who believe HGT constitutes only minor interference when inferring phylogeny. Tree of Life

17. Motivation Similarly, there are 2 types of people in the world: • And others who believe HGT has an impact on Phylogeny ( the tree-like structure of life) and the old structure should be replaced with a new net-like structure.

18. Motivation Similarly, there are 2 types of people in the world: • And others who believe HGT has an impact on Phylogeny ( the tree-like structure of life) and the old structure should be replaced with a new net-like structure.

19. Motivation • This established the aim of this experiment. • The results would be breakthrough.

20. Agenda • Terminologies • Motivation • Overview • Experiment • Conclusion

21. Overview • Horizontal Gene Transfer (HGT): • Its role in speciation, adaptation and evolution is studied intensively • Growing evidence of lateral transfer of genes among species.

22. Overview Debate: • Whole-Genome analysis of different prokaryotes indicate rampant HGTs. • Suggesting role of HGT to be: • Pivotal in prokaryotic evolution . • To be considered essence of Phylogeny. • Therefore life history cannot be well represented by tree-like form, but rather a network-like form.

23. Overview Debate: • Therefore life history cannot be well represented by tree-like form, but rather a network-like form.

24. Overview Debate: • Therefore life history cannot be well represented by tree-like form, but rather a network-like form.

25. Overview Unresolved issues in the debate : • Estimation of HGT Frequency. • Thus, inferring its impact on phylogeny. And the experiment conducted by our authors is to deal with them.

26. Overview Suggested HGT frequency: • At 24% in Thermatoga • A range up to 17% among different prokaryotes Led some researchers to believe absence of tree-like structure.

27. Overview Other researchers propose: • HGT constitutes only minor interference when inferring phylogeny.

28. Overview Other researchers propose: • HGT constitutes only minor interference when inferring phylogeny. • Methods for inferring HGT have various problems leading to Over-estimation • E.g. : Different methods of estimation gave different HGT candidates applied to same genome.

29. Overview Other researchers propose: • HGT constitutes only minor interference when inferring phylogeny. • Methods for inferring HGT have various problems leading to Over-estimation • E.g. : Different methods of estimation gave different HGT candidates applied to same genome. • Phylogeny can be sufficiently retrieved via a core of genes that may be resistant to HGT

30. Overview Inference of HGT can be done by tree comparisons. But it should be done under a proper statistical framework. Even though, if HGT events are randomly distributed across lineage: there still exist a backbone tree structure.

31. Agenda • Terminologies • Motivation • Overview • Experiment • Conclusion

32. Experiment Specific questions asked in this paper are: • What is the fundamental structure of the whole-genome (W-G) tree?

33. Experiment Specific questions asked in this paper are: • What is the fundamental structure of the whole-genome (W-G) tree? • How do individual gene trees differ from this tree, especially in terms of general HGT events? • How do individual gene trees differ from one another in terms of HGT? • What is the rate of HGT events per genome? • What kind of genome-specific patterns or gene-specific patterns are evident for HGT events? 

34. Experiment Specific questions asked in this paper are: • What is the fundamental structure of the whole-genome (W-G) tree? • How do individual gene trees differ from this tree, especially in terms of general HGT events?

35. Experiment Specific questions asked in this paper are: • What is the fundamental structure of the whole-genome (W-G) tree? • How do individual gene trees differ from this tree, especially in terms of general HGT events? • How do individual gene trees differ from one another in terms of HGT?

36. Experiment Specific questions asked in this paper are: • What is the fundamental structure of the whole-genome (W-G) tree? • How do individual gene trees differ from this tree, especially in terms of general HGT events? • How do individual gene trees differ from one another in terms of HGT? • What is the rate of HGT events per genome?

37. Experiment Specific questions asked in this paper are: • What is the fundamental structure of the whole-genome (W-G) tree? • How do individual gene trees differ from this tree, especially in terms of general HGT events? • How do individual gene trees differ from one another in terms of HGT? • What is the rate of HGT events per genome? • What kind of genome-specific patterns or gene-specific patterns are evident for HGT events? 

38. Experiment Figure 1. Flowchart of the HGT Inference Procedure Ge F, Wang L-S, Kim J (2005) The Cobweb of Life Revealed by Genome-Scale Estimates of Horizontal Gene Transfer. PLoSBiol 3(10): e316. doi:10.1371/journal.pbio.0030316

39. Experiment: Step 1 High Quality Clusters of Orthologous Groups (COGs)

40. Experiment: Step 1 Figure 1. Flowchart of the HGT Inference Procedure Use the COG database to assemble a set of high-quality orthologous groups for tree inference. Ge F, Wang L-S, Kim J (2005) The Cobweb of Life Revealed by Genome-Scale Estimates of Horizontal Gene Transfer. PLoSBiol 3(10): e316. doi:10.1371/journal.pbio.0030316

41. Experiment: Step 1 • The COG database used, covered 43 microorganisms. • Stringent high-quality COG selection procedure resulted in: • Retention of only 297 out of 3852 COG entries. • These covered 40 genomes and on average ~16 genomes/entry.

42. Step 1: Outcome Table 1. Number of COG Entries That Contain Each of 40 Genomes Ge F, Wang L-S, Kim J (2005) The Cobweb of Life Revealed by Genome-Scale Estimates of Horizontal Gene Transfer. PLoSBiol 3(10): e316. doi:10.1371/journal.pbio.0030316

43. Experiment: Step 2 High-Quality Gene Groups and the W-G Tree

44. Experiment: Step 2 Figure 1. Flowchart of the HGT Inference Procedure Construct the W-G tree that represents the best treelike description for the genealogical relationship of the genomes. Ge F, Wang L-S, Kim J (2005) The Cobweb of Life Revealed by Genome-Scale Estimates of Horizontal Gene Transfer. PLoSBiol 3(10): e316. doi:10.1371/journal.pbio.0030316

45. Experiment: Step 2 Figure 1. Flowchart of the HGT Inference Procedure Construct the W-G tree that represents the best treelike description for the genealogical relationship of the genomes. We estimate a tree for each orthologous group (gene tree) Ge F, Wang L-S, Kim J (2005) The Cobweb of Life Revealed by Genome-Scale Estimates of Horizontal Gene Transfer. PLoSBiol 3(10): e316. doi:10.1371/journal.pbio.0030316

46. Experiment: Step 2 • Use of median tree estimator designed by Kim and Salisbury to approximate W-G tree. • It is robust • Overcomes major genetic distortions like HGTs

47. Step 2: Outcome Figure 2. The W-G Tree Based on the Median Tree Algorithm Ge F, Wang L-S, Kim J (2005) The Cobweb of Life Revealed by Genome-Scale Estimates of Horizontal Gene Transfer. PLoSBiol 3(10): e316. doi:10.1371/journal.pbio.0030316

48. Step 2: Outcome • Branches with bootstrap scores <50% were collapsed into the polytomous form. • Three domains of life are shown as • (A) Archaea, • (B–J) Bacteria, and • (K) Eukaryote. • Taxonomy labels are: • Euryarchaea, • Proteobacteria, • Chlamydiae, • Spirochaetes, • Thermotogae • Aquificae, • Actinobacteria, • Deinococcus, • Cyanobacteria, • Firmicutes, and • Fungi.

49. Step 2: Outcome Figure 2. The W-G Tree Based on the Median Tree Algorithm Inferred HGT rates: red, >4%; yellow, 3%–4%; pink, 2%–3%; blue, 1%–2%; green,<1%. Ge F, Wang L-S, Kim J (2005) The Cobweb of Life Revealed by Genome-Scale Estimates of Horizontal Gene Transfer. PLoSBiol 3(10): e316. doi:10.1371/journal.pbio.0030316

50. Experiment: Step 3 & 4 HGT events for a particular gene or sequence can be detected by comparing the estimated gene tree against: • Other gene trees, or • Some candidate tree that represents the history of the genomes (W-G Tree)