Globins

Globin diversity

• Hemoglobins (, etc)

• Myoglobins (muscle)

• Neuroglobins (in CNS)

• Invertebrate globins

• Leghemoglobins

• flavohemoglobins

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

Introductory Analysis

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.

Relationships between characters

Identity

Similarity

Homology

Relationships between characters

Identity binary measured

Similarity continuousmeasured

Homology binaryinferred

Homology is relative

Are the wing of a bird and the wing of a bat homologous structure?

Homology is relative

Are the wing of a bird and the wing of a bat homologous structure?

YES

&

NO

Homology is relative

Are the wing of a bird and the wing of a bat homologous structure?

YES - as forelimbs

&

NO - not as wings

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)

Challenge 1

• Sketch an evolutionary tree that includes the following 4 genes:– Human Hb - chain– Human Hb - chain– Rabbit Hb - chain– Rabbit Hb - chain

Challenge 2

• Describe the pairwise relationships between the 4 molecules:– Human Hb - chain– Human Hb - chain– Rabbit Hb - chain– Rabbit Hb - chain

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.

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

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.

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