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

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
# of genes
Prokaryotes
Haemophilus
influenzae
1790
E. coli
5380
Yeast
6000
Nematode
19,700
Fruitfly
13,770
Ciona intestinalis 10,990
(Sea squirt)
Eukaryotes
Chicken
17,710
Human
22,200
Family size
Yeast
1
4,768 (78%)
2
415
3
56
4
23
5
9
6~10
19
11~20
8
21~50
0
50~80
0
>80
0
# gene families
530
# unique gene types 5,298
C. elegans
12,858 (67%)
665
188
93
71
104
57
33
5
3
1,219
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
18S rRNAs
tRNAs
13
5380
~22,200
1
7
~300
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
X chromosome Autosome
Humans
Apes
Old World
Monkeys
?
New World
Monkeys
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.
Examples of molecules in
different odor classes
Smell
Molecule
Name
Chemical
Formula
Fruity
Ethyloctanoate
C10H20O2
Minty
Betacyclocitral
C10H13O
Shape
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 Bovine
rhodopsin 1HZX Chain A