1. Globins

2. Globin diversity Hemoglobins ( , etc) Myoglobins (muscle) Neuroglobins (in CNS) Invertebrate globins Leghemoglobins flavohemoglobins

3. Addressing the breadth of biology Molecular biology/Biochem - protein structure, cooperative interactions,Oxygen loading Physiology - disease processes, specialized Oxygen storage Development - timing and localization of expression Genetics/Evolution - conservation and diversification of sequences & functions

4. Introductory Analysis

5. Big question - What types of inferences can we make by comparative analysis It depends - In order to infer unobserved properties we need to know why we think those properties would be related.

6. Relationships between characters Identity Similarity Homology

7. Relationships between characters Identitybinary measured Similaritycontinuous measured Homologybinary inferred

10. Homology is relative Are the wing of a bird and the wing of a bat homologous structure?

11. Homology is relative Are the wing of a bird and the wing of a bat homologous structure? YES & NO

12. Homology is relative Are the wing of a bird and the wing of a bat homologous structure? YES - as forelimbs & NO - not as wings

13. Complicating Factors Not all similarity due to common ancestry (homology) is equal. Homology is further refined into: –Orthology (speciation) –Paralogy (gene duplication) –Xenology (movement between organisms)

14. Challenge 1 Sketch an evolutionary tree that includes the following 4 genes: –Human Hb -  chain  –Human Hb -  chain –Rabbit Hb -  chain –Rabbit Hb -  chain

15. Challenge 2 Describe the pairwise relationships between the 4 molecules: –Human Hb -  chain  –Human Hb -  chain –Rabbit Hb -  chain –Rabbit Hb -  chain

17. Molecules (and other features) that are common by virtue of common ancestry are homologous, while those that are similar by convergence are analogous. Among homologous molecules, those produced by gene duplication are paralogous and those separated by speciation are orthologous.

19. Hemoglobin evolution “Keeping oxygen under control while using it in energy production has been one of the great compromises struck in the evolution of life on earth” Hardison, 1999

20. Studying globins Deeply conserved molecule which can be used to reconstruct species phylogenies. Diverse gene family that can be case study for examining evolution in gene structure/function relationships. Opportunity to look at control of expression (timing, distribution, and amount) in gene evolution. Well characterized “signatures” can be used to search for other globins.

21. Complications within development Even within a single species the same molecule can assume functions in quite different developmental pathways Gene duplication generates paralogous gene families whose members can encompass an even wider range of roles Domain shuffling generates molecules with clear homology in some regions but with potentially with quite different overall function