Evolution by Gene Duplication

Wen-Hsiung Li, Ph.D.

James Watson Professor

Ecology and Evolution

University of Chicago

Topics• Increase in gene number from simple

to complex organisms

• Evolutionary significance: Why gene duplication?

• Examples of duplicate genes

• Loss of duplicate genes

• Conclusions

Fruitfly

Nematode

Ciona intestinalis

Yeast

Human

Chicken

Haemophilus influenzae

E. coli

# of genes

1790

5380

6000

19,700

13,770

10,990

17,710

22,200

(Sea squirt)

Prokaryotes

Eukaryotes

Family size Yeast C. elegans 1 4,768 (78%) 12,858 (67%) 2 415 665 3 56 188 4 23 93 5 9 71

6~10 19 104 11~20 8 57 21~50 0 33 50~80 0 5 >80 0 3

# gene families 530 1,219 # unique gene types 5,298 14,077

Why Gene Duplication?

• Producing more of the same

• Functional fine-tuning

• Functional diversity

• Creation of a new gene from a redundant duplicate

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.

No. of rRNA and tRNA genes in a genome

Genes Mitochondrion E. coli Human (mammals)

Proteins 13 5380 ~22,200

18S rRNAs 1 7 ~300

tRNAs 22 85 ~500

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.

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

Lactate dehydrogenase (LDH)

Catalyzes the conversion between lactate and pyruvate

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

Developmental sequence of five LDH isozymes in rat heart

Functional diversity

Immunoglobulins: Antibody diversity

Major Histocompatibility Complex (MHC) genes

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

                            

                                                  

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.

Enhancing or expanding existing function

Color vision genes

Hemoglobin genes

Pygmy chimp or bonobo

Trichromatic color vision

from Backhaus, 1998

400 500 600

Wavelength (nm)

A person with only a short-wave and a middle-wave photo-receptor

Vision of most mammals (dichromats)

a. Short wave opsin (blue)

b. Long or middle wave opsin (red/green)

X-linked autosome

Origin of routine trichromacy

New World Monkeys

Humans

Apes

Old World Monkeys

X chromosome Autosome

?

Hemoglobin

In human and mammals: A tetramer consisting of two α

and two β globin chains

In jawless fish: A monomer and only 1 globin gene

Polymerization occurred probably after gene duplication

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.

                                     

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

Monomer

Monomer

Creation of a new gene from a redundant duplicate gene

Myoglobin and hemoglobin

Trypsin and chymotrypsin

Olfactory receptors

Hox genes

Pax genes

Hemoglobin: Oxygen carrier in blood.

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

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.

~1,500 million years ago

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.

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.

SmellMolecule Name

Chemical Formula

Shape

FruityEthyl-octanoate

C10H20O2                

MintyBeta-cyclocitral

C10H13O                

Examples of molecules in different odor classes

Minty p-anisaldehyde C8H8O2

               

Nutty,Medicinal

2,6-dimethyl pyrazine

C6H8N2

               

Nutty,Medicinal

4-heptanolide C7H12O2

               

Nutty,Medicinal

p-cresol C7H8O

               

Putative Binding cavity in Human OR1.04.06

Binding cavity for retinal in Bovinerhodopsin 1HZX Chain A