Evolution by Gene Duplication

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Evolution by Gene Duplication

• Wen-Hsiung Li, Ph.D.
• James Watson Professor
• Ecology and Evolution
• University of Chicago

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Topics

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

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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
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Why Gene Duplication?

• Producing more of the same
• Functional fine-tuning
• Functional diversity
• Creation of a new gene from a redundant duplicate

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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.

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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

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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.

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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

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

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Developmental sequence of five LDH isozymes in
rat heart
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Functional diversity

• Immunoglobulins Antibody diversity
• Major Histocompatibility Complex (MHC) genes

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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

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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.
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Enhancing or expanding existing function

• Color vision genes
• Hemoglobin genes

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Pygmy chimp or bonobo
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Trichromatic color vision
from Backhaus, 1998
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Wavelength (nm)
A person with only a short-wave and a middle-wave
photo-receptor
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• Vision of most mammals (dichromats)
• a. Short wave opsin (blue)
• b. Long or middle wave opsin (red/green)

X-linked autosome
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Origin of routine trichromacy
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Hemoglobin

• In human and mammals
• A tetramer consisting of two a and two ß
  globin chains
• In jawless fish
• A monomer and only 1 globin gene
• Polymerization occurred probably after gene
  duplication

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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.

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Types of hemoglobin in humans

• In the embryo ?2e2 and a2e2
• In the fetus Hemoglobin F (a2?2)
• In adults
• Hemoglobin A (a2ß2) - Most common type
• Hemoglobin A2 (a2d2) - d chain synthesis
  begins late in the third trimester and in adults,
  it has a normal level of 2.5
• Hemoglobin F (a2?2) - In adults it is
  restricted to a limited population of red cells

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Monomer
Monomer
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Creation of a new gene from a redundant duplicate
gene

• Myoglobin and hemoglobin
• Trypsin and chymotrypsin
• Olfactory receptors
• Hox genes
• Pax genes

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

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1,500 million years ago
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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.

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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.
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Examples of molecules in different odor classes

Smell Molecule Name Chemical Formula Shape
Fruity Ethyl-octanoate C10H20O2                
Minty Beta-cyclocitral C10H13O                

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Minty p-anisaldehyde C8H8O2                
Nutty,Medicinal 2,6-dimethyl pyrazine C6H8N2                
Nutty,Medicinal 4-heptanolide C7H12O2                
Nutty,Medicinal p-cresol C7H8O                
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Putative Binding cavity in Human OR1.04.06
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Binding cavity for retinal in Bovinerhodopsin
1HZX Chain A