Gene Duplication

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Gene Duplication
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Gene Duplication - History
1936 The first observation of a duplicated gene
was in the Bar gene of Drosophila. 1950 Alpha
and beta chains of hemoglobin are recognized to
have been derived from gene duplication 1970
Ohno developed a theoretical framework of gene
duplication 1995 Gene duplications are studied
in fully sequenced genomes
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Types of Genomic Duplications

• Part of an exon or the entire exon is duplicated
• Complete gene duplication
• Partial chromosome duplication
• Complete chromosome duplication
• Polyploidy full genome duplication

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Mechanism of Gene Duplication
Genes are duplicated mainly due to unequal
crossing over
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Mechanism of Gene Duplication
If these regions are complementary, it increases
the chance of unequal crossing over. For example,
if both of these regions are the same repeated
sequence (microsatellite, transposon, etc)
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After a Gene is Duplicated

• Alternative fates
• It can die and become a pseudogene.
• It can retain its original function, thus
  allowing the organism to produce double the
  amount of the derived protein.
• The two copies can diverge and each one will
  specialize in a different function.

Identical copies
One copy dies
Divergence
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Invariant repeats
If the duplicated genes are identical or nearly
identical, they are called invariant repeats.
Many times the effect is an increase in the
quantity of the derived protein, and this is why
these duplications are also called dose
repetitions. Classical examples are the genes
encoding rRNAs and tRNAs needed for translation.
Invariant repeats
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Duplications of RNA-specifying genes
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rRNA
Ribosome is a complex of proteins and RNA (called
rRNA) on which proteins are built, based on the
information in the mRNA. Ribosomes are always
composed of two units big and small.
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rRNA
In prokaryotes the entire ribosome is 70S, and is
composed of a 50S large subunit, and a 30S small
subunit. In eukaryotes the entire ribosome is
80S, and is composed of a 60S large subunit and a
40S small subunit. The S value is the
sedimentation coefficient in ultracentrifuge.
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rRNA
There are also ribosomal genes coded by the
mitochondrial genome. In fact, the mitochondrial
ribosome is coded by both nuclear and
mitochondrial genes.
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Correlation between the number of rRNA genes and
the genome size
Numbers of rRNA and tRNA genes per haploid genome
in various organisms _____________________________
_____________________________________________ Geno
me Source Number of Number
of Approximate rRNA sets tRNA
genesa genome size (bp) __________________________
________________________________________________ H
uman mitochondrion 1 22 2 ?
104 Nicotiana tabacum chloroplast 2
37 2 ? 105 Escherichia coli 7
100 4 ? 106 Neurospora crassa 100
2,600 2 ? 107 Saccharomyces cerevisiae 140
360 5 ? 107 Caenorhabditis elegans 55
300 8 ? 107 Tetrahymena thermophila 1
800c 2 ? 108 Drosophila melanogaster 120-240
590-900 2 ? 108 Physarum polycephalum 80-280
1,050 5 ? 108 Euglena gracilis 800-1,000
740 2 ? 109 Human 300 1,300 3 ?
109 Rattus norvegicus 150-170 6,500 3 ?
109 Xenopus laevis 500-760 6,500-7,800 8 ?
109 ______________________________________________
____________________________
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Correlation between number of rRNA genes and
genome size an exception
Numbers of rRNA and tRNA genes per haploid genome
in various organisms _____________________________
_____________________________________________ Geno
me Source Number of
Approximate rRNA sets
genome size (bp) _______________________________
___________________________________________ Human
mitochondrion 1 2 ?
104 Nicotiana tabacum chloroplast 2
2 ? 105 Escherichia coli 7 4 ?
106 Neurospora crassa 100 2 ?
107 Saccharomyces cerevisiae 140 5 ?
107 Caenorhabditis elegans 55 8 ?
107 Tetrahymena thermophila 1 2 ?
108 Drosophila melanogaster 120-240 2 ?
108 Physarum polycephalum 80-280 5 ?
108 Euglena gracilis 800-1,000 2 ?
109 Human 300 3 ? 109 Rattus
norvegicus 150-170 3 ? 109 Xenopus
laevis 500-760 8 ? 109 ___________________
__________________________________________________
_____
The general pattern bigger genomes ? more genes
to transcribed ? more rRNA needed.
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Variant repeats
Some classic examples Trypsin, the digestive
enzyme and Thrombin (cleaves fibrinogen during
blood clotting) were derived from a complete gene
duplication. Lactalbumin, connected with lactose
synthesis and Lysozyme, which degrades bacteria
cell wall are also a result of an ancient gene
duplication.
Variant repeats
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Vision. The Opsins stories
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Cones and Rods
There are two types of photoreceptor cells in the
human retina, rods and cones.
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Cones and Rods
Rod cells are responsible for vision at low light
levels (scotopic vision). They do not mediate
color vision, and have a low spatial acuity
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Cones and Rods
Cone cells are active at higher light levels
(photopic vision). They are capable of color
vision and are responsible for high spatial
acuity
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Colors
There are 3 types of pigments in cones. Their
peaks of absorption are at about 430, 530, and
560 nanometers.
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Colors
The cones are loosely called "blue", "green",
and "red. loosely because 1. the names
refer to peak sensitivities (which in turn are
related to the ability to absorb light) rather
than to the way the pigments would appear if we
were to look at them.
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Colors
The cones are loosely called "blue", "green",
and "red. loosely because 2. Monochromatic
lights whose wavelengths are 430, 530, and560
nanometers are not blue, green, and red but
violet, blue-green, and yellow-green
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Terminology
Terminology is almost impossible to change.Some
call the cones just long, middle, and short.
An impossible elephant
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Opsin and retinal
Each photopigment consists of two parts a
protein called opsin and a lipid derivative
called retinal.
The opsin is a member of the superfamily of
G-protein coupled receptors. The opsins
sequence determines the absorbance
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Opsin Genetics
The blue opsin is encoded by an autosomal
gene. The red and green opsins are encoded by
X-linked genes. There are cases in which the
green opsin is duplicated on the X
chromosome. Red and green are very similar in
amino-acid sequence (96). Blue is more diverged
(43). Blue diverged about 500 mya (million
years ago). Red and green diverged only 25-35 mya.
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Opsin Genetics
Indeed new-world monkeys have only one X-linked
pigment, so the divergence of green and red
occurred after the divergence of new-world
monkeys from old-world monkeys. Thus, old-world
monkeys are trichromatic.
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Opsin Genetics
New-world monkeys have only one X-linked locus
(except for the howler monkey from the Alouatta
genus).
howler monkey
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Opsin Genetics
But the X-linked locus in the new world monkeys,
such as for squirrel monkeys and tamarins, can be
highly polymorphic, with some alleles similar to
the red opsin and some to the green.
Thus, a female can be trichromatic (if
heterozygous) but males are always
dichromatic. Dichromatic monkeys cannot
distinguish between red and green.
Squirrel monkeys
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Ishihara Plates are you color blind?
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The individual with normal color vision will see
the number 5 revealed in the dot pattern. An
individual with Red/Green (the most common) color
blindness will see the number 2 revealed in the
dots
5 or 2?
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Opsin conclusion one
Old world monkeys achieved trichomatic vision by
a mechanism akin to isozymes (different proteins
coded by different loci). Heterozygous female
squirrel monkeys achieved trichomatic vision by
using two allozymes (distinct proteins encoded
by different allelic forms at a single
locus). The polymorphism is probably a form of
overdominant selection.
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Opsin selective advatage?
The selective advantage of trichromatic vision is
thought to be the ability to detect ripe fruits
against a background of dense green foliage.
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Ortholog, Paralog
Mouse 1
Two independent duplications
Mouse 2
Rat 1
Rat 2
Human 1

• Rat 1 is orthologous to Mouse 1 and to Mouse 2
• Rat 2 is orthologous to Mouse 1 and to Mouse 2
• Mouse 1 and Mouse 2 are paralogous
• Rat 1 and Rat 2 are paralogous
• Human 1 is orthologous to all other genes.

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Ortholog, Paralog
Mouse 1
One duplications
Rat 1
Mouse 2
Rat 2
Human 1

• Rat 1 is paralogous to Mouse 2 and to Rat 2
• Mouse 1 is paralogous to Mouse 2 and to Rat 2
• Mouse 1 and Rat 1 are orthologous
• Mouse 2 and Rat 2 are orthologous
• Human 1 is orthologous to all other genes.

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Ortholog, Paralog
Mouse 1
Rat 1
Mouse 2
Rat 2
Human 1
Orthologous genes are usually more similar in
terms of function than paralogous ones!
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Organisms Have a Complicated Hierarchy
Canis familiaris. Common name Dog. The
species familiaris Genus Canis. Family
Canidae. Order Carnivora. Class Mammalia.
Phylum Chordata. Kingdom Metazoa
Multi-cellular organism
First letter always in capital
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Genes Have a Much Simpler Classification
If the sequence similarity is at least 50 it is
of the same family. If it is less than 50 it is
considered to be of the same superfamily.
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The Globins
The alpha globins are one family, the beta
globins are another family. Alpha and beta
globins, together with myoglobin are part of the
globin superfamily.
Another super family
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Theory and Reality
The strict 50 criterion is not always
appropriate. Usually, other considerations such
as function, tissue specificity and type of
homology are also taken into account.
Theory
Reality