1. Two Component Systems Sequence Characteristics Identification in Bacterial Genome Yaw-Ling Lin Dept Computer Sci. & Info. Management, Providence University, Taichung, Taiwan.

2. Yaw-Ling Lin, Providence, Taiwan2 Two-Component System Two-component systems (2CS): –Sensor histidine kinase –response regulator The major controlling machinery in order for bacteria to encounter a diverse and often hostile environment

3. Yaw-Ling Lin, Providence, Taiwan3 2CS in Pseudomonas aeruginosa PAO1 http://www.pseudomonas.com/ “Complete genome sequence of Pseudomonas aeruginosa PAO1, an opportunistic pathogen.” Nature. 2000 Aug 31;406(6799):947-8. by Stover CK, Pham XQ, Erwin AL, et al. Genome: 6.3M bp predicted genes: 5570 123 genes were classified as 2CSs.

4. Yaw-Ling Lin, Providence, Taiwan4 2CS in PAO1

5. Yaw-Ling Lin, Providence, Taiwan5 2CS in PAO1

6. Yaw-Ling Lin, Providence, Taiwan6 2CS in PAO1

7. Yaw-Ling Lin, Providence, Taiwan7 2CS in PAO1 There are 123 annotated 2CS genes in PAO1. Use systemic analysis of the evolutionary relationships between the sensor kinase and response regulator of a 2CS. Construct phylogenic trees using Clustal-W for 54 sensor kinases and 59 response regulators.

8. Yaw-Ling Lin, Providence, Taiwan8 2CS in PAO1 -- Sensor Tree

9. Yaw-Ling Lin, Providence, Taiwan9 2CS: Regulator Tree

10. Yaw-Ling Lin, Providence, Taiwan10 Subtrees Analysis of 2CS

11. Yaw-Ling Lin, Providence, Taiwan11 Co-evolution subtree Analysis SensOr TreeRegulator Tree versus

12. Yaw-Ling Lin, Providence, Taiwan12 Distance Function

13. Yaw-Ling Lin, Providence, Taiwan13 Algorithm AGR

14. Yaw-Ling Lin, Providence, Taiwan14 k-agreement Problem

15. Yaw-Ling Lin, Providence, Taiwan15 k-agreement: Algorithm Subtree sum: stored the numbers of leaves on the internal node --- bottom-up, O(n) time Bucket sort the internal nodes --- O(n) time Identifies the subtrees of T 1 with k leaves, say A 1 to A p. --- O(n) time Identifies the subtrees of T 2 with k leaves, say B 1 to B q. --- O(n) time Cross checking A 1 to A p and B 1 to B q --- O(n) time

16. Yaw-Ling Lin, Providence, Taiwan16 Co-evolution sensor/regulator Trees 46 paired clustered sensors and regulators Six groups of 2CS genes were identified -Group A: 2CS sensor genes PA1335, PA5166 and PA5511 and their linked regulator genes PA1336, PA5165, and PA5512 are apparently co-evolved from a common ancestor. The PA5165/PA5166 pair is happened to split earlier than the PA1335/PA1336 and PA5511/PA5512. -Group B, E and F each containing two 2CS operons are probably also evolved by gene cluster duplication. -Group C contained Bordetella parapertussis bvgAS-like gene clusters PA3044/PA3045 and PA3946/PA3947/PA3948. -Ggroup D, the gene clusters PS2571/PA2572 and PA2882/PA2881 appeared to be perfectly co-evolved.

17. Yaw-Ling Lin, Providence, Taiwan17 Co-evolution Tree Analysis

18. Yaw-Ling Lin, Providence, Taiwan18 Co-evolution Tree Analysis

19. Yaw-Ling Lin, Providence, Taiwan19 Correlation analysis Does gene duplication tend to occur within a relative short distance on a bacterial genome? Idea: a dot-matrix plot will be created, with the X- axis being the physical distance, and Y-axis being the evolutionary distance, between two comparing 2CS. Some subset of 2CS, presumably functionally related, could possess the correlation between their physical and evolutionary distances.

20. Yaw-Ling Lin, Providence, Taiwan20 k-correlation Problem

21. Yaw-Ling Lin, Providence, Taiwan21 k-correlation is NP-complete Let M 1 be an adjacent matrix of a graph G, and M 2 be an zero matrix. If we can solve the k-correlation problem in polynomial time, then the maximum independent set problem will be polynomial solvable.

22. Yaw-Ling Lin, Providence, Taiwan22 Conclusion Identifying novel 2CS in other bacteria genomes as well as in eucaryotic genomes Clustering analysis of 2CS for functional prediction of uncharacterized genes Co-evolutionary analysis of 2CS

23. Yaw-Ling Lin, Providence, Taiwan23 Future Research Identifying novel 2CS in other bacteria genomes as well as in eucaryotic genomes Clustering analysis of 2CS for functional prediction of uncharacterized genes Co-evolutionary analysis of 2CS