Download BIOL 504: Molecular Evolution

BIOL 504: Molecular Evolution
Gene Duplication
Gene duplication
Gene duplication is a primary means by which
new genes can arise
Dr. Erica Bree Rosenblum
Gene duplication
Types of gene duplication
1) 
2) 
3) 
4) 
5) 
Partial (internal) internal gene duplication
Complete gene duplication
Partial chromosomal duplication
Complete chromosomal duplication
Whole genome duplication
Exon duplication
Gene duplication
Principle mechanism for gene duplication is
unequal crossing over
Unequal crossing over is facilitated by
repetitive sequences
So gene duplications (particularly those in
tandem) can beget more duplications
Exon duplication
Eukaryotic genes contain many exons
Exon duplication can be advantageous by:
Neighboring exons are often very similar
suggesting history of exon duplications
a)  Enhancing number of functional or
structural domains so the protein can
perform existing functions better/faster
Exon duplication is major mechanism for
gene elongation and evolution of complexity
b)  Decreasing constraint on one exon copy
allowing development of new functions
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Exon duplication
Example: antifreeze genes in fish
Freezing of Antarctic ocean ~10-14 MYA
Antifreeze glycoprotein gene ~5-14 MYA
Many duplication events in short time period
likely under strong positive selection
Exonization
Exons can appear and disappear in processes
other than shuffling
Exonization: process by which intronic sequence
become exons - not very common
Pseudoexonization: process by which exon (not
whole gene) becomes nonfunctional
Gene duplication
Gene duplication can result in a copy that:
a)  becomes a functionless pseudogene (most
duplicate genes have a “half-life” of only a
few million years)
b)  retains its original function (these
invariant repeats can enable dose effects
by allowing more protein production)
c)  develop a novel function (these variant
repeats can create new genes via
neofunctionalization)
Exon shuffling
Exon shuffling can arise from duplication,
insertion or deletion
Insertion of exons from one gene into another
can create mosaic or chimeric proteins
Example: tissue plasminogen activator (involved in
blood clotting) acquired segments from at least 4
other genes - all at exon/intron borders
Gene duplication
Rate of duplication of entire genes is only
slightly less than the rate at which nucleotide
substitutions occur at silent sites
Over 250 million years, nearly every gene in a
typical eukaryotic genome can be expected to
duplicate once
So gene duplication can be a major
evolutionary consideration
Gene duplication
Generally people talk about gene copies that develop
new constraints because selection is relaxed but…
a)  This only works if new function can evolve via few
substitutions (or it is more likely to become a
nonfunctional pseudogene)
b)  Evidence from tetraploid genomes suggests
copies are still under purifying selection
c)  Functionally distinct copies often arise from
positive selection
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Gene duplication
Gene duplication
So how does gene duplication lead to new functions?
So how does gene duplication lead to new functions?
Neofunctionalization
Neofunctionalization
Masking effects
Masking effects
Subfunctionalization
Subfunctionalization
Note that most new gene copies will NOT develop
splashy new functions - most will become
nonfunctional. Nonfunctionalization or silencing
of a gene due to deleterious mutation produces a
pseudogene and can result in gene loss
Neofunctionalization
Neofunctionalization: one copy acquires a
beneficial mutation that results in a new function
Ancestral polymorphisms can also facilitate
neofunctionalization
Example: insecticide resistance in mosquito.
Acetylcholinesterase enzyme plays essential role in central
nervous system. Mutant allele at duplicate gene copy
confers insecticide resistance but comes at a fitness cost in
insecticide free environments. Maintained at very low
frequency in normal populations but linked combo of wildtype and resistant alleles appear in exposed populations.
Subfunctionalization
Subfunctionalization: partitioning of ancestral gene
functions to duplicate genes through complementary
loss-of-function mutations in paralogous copies
One copy becomes fixed for a mutation that
eliminates an essential subfunction, permanently
preserving the second copy. Loss of alternate
subfunction in second copy then reciprocally
preserves the first copy
Masking effects
Masking effect: duplicate genes have selective
advantage associated with their ability to mask the
effects of deleterious mutations
However in practice there is not much evidence to
support this route to new gene functions
Gene duplication
Model for subfunctionalization
Single gene encodes
multifunctional protein
Gene duplication
Each copy specializes
for one function
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Gene duplication
Subfunctionalization
Lots of evidence for subfunctionalization
duplication
Studies on polyploid fish repeated show tissue
specificity of duplicated enzyme loci
degeneration
Zebrafish retains 25% of its
original gene pairs in
functional state
complementation
subfunctionalization
neofunctionalization
nonfunctionalization
Subfunctionalization
Subfunctionalization
Lots of evidence for subfunctionalization
Quantitative subfunctionalization: when total capacity
of both loci is degraded such that their joint presence
is needed to fulfill role of ancestral gene
Studies on polyploid fish repeated show tissue
specificity of duplicated enzyme loci
Example: Cytochrome P450
copies, one expressed in
ovary and other in brain.
Orthologous single-copy gene
in tetrapods expressed in
both tissues
Gene families
Gene family: all genes belonging to a certain
group of repeated sequences - often lie on the
same chromosome
Gene family expansions (chytrid fungus)
Fungalysin metallopeptidase
Serine protease
Supergene family: more distantly related gene
copies - generally <50% aa similarity
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Gene family expansions (chytrid fungus)
Fungalysin metallopeptidase
Serine protease
Gene families
Can have few or many repeats in a genome
Example: rRNA and tRNA genes can exhibit
hundreds or thousands of copies and vary by species
= Up
= Down
Bold font: up in sporangia
Boxes: up in zoospores
Gene families
Gene families
Evolution of opsins allow wide-range of color detection
blue
autosomal
red
X-linked
green
X-linked
Gene families
African cichlids have eight opsin genes from rapid
multiple duplication events - each opsin codes for
distinct visual pigment and positive selection has
been detected for most
autosome
X-linked
Human
Tricromatic
New world
monkeys
Dicromatic
Gene families
Further, adaptation to different light
environments In turbid lakes (like Lake
Victoria) where red light is transmitted more
easily, selection on the red-sensitive opsin
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Gene families
Gene duplication and adaptation
This all can effect mate choice!
Salivary amylase gene (AMY1) and starch consumption
Perry et al 2007 Nature Genetics
Gene duplication and speciation
Ancestral species
Gene duplication
Geographic isolation
and divergent gene
silencing
Hybridization
Other ways of producing new functions
In addition to exon shuffling and gene duplication,
new genes/proteins can be produced through:
1) Overlapping genes
2) Alternative splicing
3) Intron-encoded and nested genes
4) Functional convergence
5) RNA editing
6) Gene sharing
Nonfunctional gametes
Other ways of producing new functions
Other ways of producing new functions
In addition to exon shuffling and gene duplication,
new genes/proteins can be produced through:
In addition to exon shuffling and gene duplication,
new genes/proteins can be produced through:
1)  Overlapping genes: DNA segment coding for
multiple products using different reading
frames, start codons or complementary strands
1)  Overlapping genes
2) Alternative splicing
3) Intron-encoded and nested genes
4) Functional convergence
5) RNA editing
6) Gene sharing
2) Alternative splicing: production of different
mRNAs from same DNA
3) Intron-encoded and nested genes
4) Functional convergence
5) RNA editing
6) Gene sharing
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Other ways of producing new functions
In addition to exon shuffling and gene duplication,
new genes/proteins can be produced through:
Other ways of producing new functions
In addition to exon shuffling and gene
duplication, new genes/proteins can be produced
through:
1)  Overlapping genes
2) Alternative splicing: production of different
mRNAs from same DNA
example: doublesex gene in Drosophila
alternatively spliced in females (exons 1,2,3,4)
and males (exons 1,2,3,5,6)
1) Overlapping genes
2) Alternative splicing
3) Intron-encoded and nested genes:
genes inside of introns - either on the same or
opposite strand
4) Functional convergence
5) RNA editing
6) Gene sharing
Other ways of producing new functions
Other ways of producing new functions
In addition to exon shuffling and gene
duplication, new genes/proteins can be produced
through:
In addition to exon shuffling and gene
duplication, new genes/proteins can be produced
through:
1) Overlapping genes
2) Alternative splicing
3) Intron-encoded and nested genes
1) Overlapping genes
2) Alternative splicing
3) Intron-encoded and nested genes
4) Functional convergence
4) Functional convergence: convergent evolution
of protein function from unrelated genes
5) RNA editing
6) Gene sharing
Other ways of producing new functions
5) RNA editing: posttranslational modification
can alter protein product or gene expression
6) Gene sharing
Molecular tinkering
In addition to exon shuffling and gene
duplication, new genes/proteins can be produced
through:
“Many proteins that were originally considered to
be relatively recent evolutionary additions turned
out to be derived from ancient proteins…
1) Overlapping genes
2) Alternative splicing
3) Intron-encoded and nested genes
4) Functional convergence
5) RNA editing
True novelty is almost unheard of during
evolution; rather, preexisting genes and parts of
genes are transformed to produce new
functions…
molecular tinkering…molecular opportunism”
6) Gene sharing: gene acquires and maintains a
second function - may require changes in
regulation (tissue or developmental timing)
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