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Presented by Jennelle Heyer and Jonathan Ebbers December 7, 2004

Protein Modularity and Evolution : An examination of organism complexity via protein domain structure. Presented by Jennelle Heyer and Jonathan Ebbers December 7, 2004. Presentation Outline. Background Material - Protein Evolution, Theory of Domains, Gene Number

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Presented by Jennelle Heyer and Jonathan Ebbers December 7, 2004

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  1. Protein Modularity and Evolution:An examination of organism complexity via protein domain structure Presented by Jennelle Heyer and Jonathan Ebbers December 7, 2004

  2. Presentation Outline • Background Material - Protein Evolution, Theory of Domains, Gene Number • Hypothesis - Using a model protein family • Procedure/Methods - DPIP Program, Phylogenic Analysis • Results • Discussion/Conclusions

  3. Theories of Protein Evolution A long time ago, in the primodial soup of life, small polypeptides began to form… HDLC or TCP or…. HDLC + TCP = HCLCTCP HCI*CTCP + TCP… Functional proteins HDLC or TCP or…. HDLC + TCP = HCLCTCP HCI*CTCP + QZX… Functional proteins

  4. Concept of Modularity • Proteins consist of one or more domains that were pieced together over time • Domain  building blocks of proteins • Defined as “spatially distinct structures that could conceivably fold and function in isolation” (Pontig and Russell, 2002) • Dictate the function of the protein • Evolutionary pressure to conserve (sequence and/or structure)

  5. Organismal Complexity • The nematode, C. elegans, has 19,500 genes in its genome • Humans have between 20,000 and 25,000 genes in their genome • HOW CAN THAT BE? • Alternate splicing, multi-functional/network proteins

  6. Hypothesis • Gene products, proteins, can be multi-functional with the introduction of domains • “…evolution does not produce innovation from scratch. It works on what already exists, either transforming a system to give it a new function or combining several systems to produce a more complex one” (Jacob, 1946) • More complex or phylogenetically derived organisms produce proteins with greater domain complexity

  7. Hypothesis Part II • Create a protein domain “tool” • Position • Partner domain • General organization • Protein evolution • Using a variety of sequenced genomes • Allow investigators to learn about domain of interest and apply to research

  8. Kinesins: A model protein family • Motor proteins found in eukaryotic organisms • Contain a conserved motor domain • Bind and walk along microtubules • Can carry a variety of “cargo” • May contain multiple domains http://www.mb.tn.tudelft.nl/projects/

  9. Kinesins: A model protein family • Arabidopsis thaliana, a model plant species, contains 61 kinesins • S. pombe –10, C. elegans –22, Drosophlia –25, Human and mouse ~ 45 From Reddy and Day, 2001

  10. Programming Approach • Two programs used, BLAST and InterProScan, held together with perl scripts • Give a domain sequence to PSI-BLAST, which will identify proteins that have that domain. • One by one, give those protein sequences to IPR, which identifies domains in the protein. • Create a listing of proteins and map the data into a phylogeny. • Create a tree based on the phylogeny and domains

  11. Program Flowchart Domain Sequence BLAST List of proteins with similar domains InterProScan Maketree List of domains in every protein Tree (includes domains)

  12. Program Details • Database selection: • BLAST: Refseq over nr • InterProScan: SMART database, only • Threshold values: • BLAST: Option to change, improve resolution • InterProScan: E-value at 0.99, up from 0.01 • Used Arabidopsis sequences as a control • Name: DPIP (Domain Placement in Proteins)

  13. Results • A Quick Look at the Data • Phylogenetic Approach • Hypothesis I • Qualitative Approach • Hypothesis II

  14. A Quick L k

  15. Phylogenetic Approach • “More complex or phylogenically derived organisms produce proteins with greater domain complexity” • Trace domain characteristics on a preset tree • Use MacClade tree drawing software • Uses input data to create most parsimonious trace • Characteristics: Maximum # domains Unique domains

  16. Maximum # of Domains per Protein Green = 1 Black = 3

  17. Number of Unique Domains per Organism Blue = 1 Pink = 2 Dk. Blue = 3 Yellow = 5 Black = 6 Dash - ???

  18. Phylogenetic Conclusions • Inconclusive or null hypothesis supported • Possible explanations: • Kinesins may have limited domain complexity due to function or folding • Inherent bias in DPIP (refseq database) • Future Work: • Testing other domains through same process • Updating database • Include measure for position (N/I/C)

  19. Qualitative Approach • Create a protein domain “tool” • Position • Partner domain • General organization • Protein evolution • Using a variety of sequenced genomes • Compile data into a more informative table

  20. - Can I trace domain or protein evolution??

  21. Presence of FHA/PH domain in kinesins Yellow – Absent Blue - Present

  22. Conclusions • DPIP program was created to answer two questions: • Does organismal complexity correspond with protein complexity? • Can we create a tool for researched to better understand domain in protein families? • For kinesins motor domains: No and Yes • For other domains:???? Thanks to Webb Miller, Richard Cyr Claude DePamphillis, Alexander Richter, Plant Physiology, Biology, and Bioinformatics Depts.

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