Evolution by Gene Duplication

1. Evolution by Gene Duplication Wen-Hsiung Li, Ph.D. James Watson Professor Ecology and Evolution University of Chicago

2. Topics • Increase in gene number from simple to complex organisms • Evolutionary significance: Why gene duplication? • Examples of duplicate genes • Loss of duplicate genes • Conclusions

3. # of genes Prokaryotes Haemophilus influenzae 1790 E. coli 5380 6000 Yeast 19,700 Nematode Fruitfly 13,770 Ciona intestinalis 10,990 (Sea squirt) Chicken 17,710 Eukaryotes Human 22,200

5. Why Gene Duplication? • Producing more of the same • Functional fine-tuning • Functional diversity • Creation of a new gene from a redundant duplicate

6. Producing more of the same The normal physiology of an organism may require many copies of a gene. Example: The translational machinery of an organism usually requires many transfer RNA (tRNA) genes and ribosomal RNA (rRNA) genes.

7. No. of rRNA and tRNA genes in a genome Genes Mitochondrion E. coli Human (mammals) Proteins 135380~22,200 18S rRNAs 1 7~300 tRNAs 22 85 ~500

8. Response to stress Multi-drug resistance (P-glycoprotein) (mdr) genes Amplification of mdr genes often occurs in cancer cells after a patient has been treated with drugs. Insecticide resistance Multiple copies of esterase genes have been found in mosquito populations treated with insecticide.

9. Functional fine-tuning Isozymes: Enzymes that catalyze the same biochemical reaction but may differ from one another in biochemical properties, tissue specificity, and developmental regulation Are encoded by duplicate genes Examples: Lactate dehydrogenase (LDH), aldolase, creatine kinase

10. Lactate dehydrogenase (LDH) Catalyzes the conversion between lactate and pyruvate

11. LDH isozymes LDH: tetramer (consisting of 4 subunits) A and B subunits are encoded by two separate genes A4, A3B, A2B2, AB3, B4 B4, AB3: function better in aerobic tissues such as heart A4, A3B: function better in anaerobic tissues such as skeletal muscle

12. Developmental sequence of five LDH isozymes in rat heart

13. Functional diversity Immunoglobulins: Antibody diversity Major Histocompatibility Complex (MHC) genes

14. Immunoglobulins Immunoglobulin: 2 light chains and 2 heavy chains 2 types of light chain: kappa & lambda 5 types of heavy chain: mu, delta, gamma (4 subtypes), epsilon and alpha. The type of heavy chain defines the class of immunoglobulin: IgM, IgD, IgG, IgE and IgA

17. Over 15,000,000 combinations of Variable, Diversity and Joining gene segments are possible. Imprecise recombination and mutation increase the variability into billions of possible combinations.

18. Enhancing or expanding existing function Color vision genes Hemoglobin genes

21. Pygmy chimp or bonobo

22. Trichromatic color vision from Backhaus, 1998

23. 400 500 600 Wavelength (nm) A person with only a short-wave and a middle-wave photo-receptor

24. Vision of most mammals (dichromats) a. Short wave opsin (blue) b. Long or middle wave opsin (red/green) X-linked autosome

25. X chromosome Autosome Humans Apes Old World Monkeys ? New World Monkeys Origin of routine trichromacy

27. Hemoglobin In human and mammals: A tetramer consisting of two αand two β globin chains In jawless fish: A monomer and only 1 globin gene Polymerization occurred probably after gene duplication

28. Advantages of being a tetramer Allows hemoglobin to bind oxygen in a cooperative fashion: The binding of the first oxygen molecule facilitates the binding of subsequent oxygen molecules. Conversely, release of the first oxygen molecule facilitates the release of subsequent molecules. As an oxygen carrier in blood it must load and unload oxygen molecules at the right partial oxygen pressure.

31. Types of hemoglobin in humans • In the embryo: ξ2ε2 and α2ε2 • In the fetus: Hemoglobin F (α2γ2) • In adults: Hemoglobin A (α2β2) - Most common type Hemoglobin A2 (α2δ2) - δ chain synthesis begins late in the third trimester and in adults, it has a normal level of 2.5% Hemoglobin F (α2γ2) - In adults it is restricted to a limited population of red cells

32. Monomer Monomer

33. Creation of a new gene from a redundant duplicate gene Myoglobin and hemoglobin Trypsin and chymotrypsin Olfactory receptors Hox genes Pax genes

34. Hemoglobin: Oxygen carrier in blood. Myoglobin: Oxygen carrier in tissues. It has a higher oxygen affinity than hemoglobin.

35. Trypsin and chymotrypsin Digestion of protein in the intestine is carried out by trypsin and chymotrypsin. Trypsin attacks the peptide bond at the basic amino acids lysine and arginine, whereas chymotrypsin attacks the peptide bond at the carboxyl side of the aromatic amino acids phenylalanine and tyrosine.

36. ~1,500 million years ago

37. Olfactory receptors The detection of small molecules plays an important role in the survival of most animals, which use odor to identify and evaluate their food, predators, and territory. The olfactory system is important for our quality of life. A unique odor can trigger distinct memories from our childhood or from emotional moments – positive or negative. When something tastes good it is mainly due to activation of the olfactory system.

38. The vivid world of odors: A Nobel Prize (2004) was given to Richard Axel and Linda Buck for their discoveries of odorant receptors and the organization of the olfactory system.

39. Examples of molecules in different odor classes

41. Putative Binding cavity in Human OR1.04.06

42. Binding cavity for retinal in Bovinerhodopsin 1HZX Chain A