Download (Part 2) Mutation and genetic variation

BIOE 109
Summer 2009
Lecture 4- Part I
Mutation and genetic variation
Four basic processes that can explain
evolutionary changes:
1. Mutation
2. Gene Flow
3. Genetic drift
4. Natural selection
Sources of genetic variation
1. Crossing over during meiosis- creates new
combinations of alleles on individual chromosomes
2. Independent assortment- creates new combinations
chromosomes in the daughter cells
Sources of genetic variation
1. Crossing over during meiosis- creates new
combinations of alleles on individual chromosomes
2. Independent assortment- creates new combinations
chromosomes in the daughter cells
3. Mutations- create completely new alleles and genes
General classes of mutations
General classes of mutations
Point mutations
“Copy-number” mutations
Chromosomal mutations
Genome mutations
Point mutations
Point mutations
There are four categories of point mutations:
Point mutations
There are four categories of point mutations:
1. transitions (e.g., A  G, C  T)
Point mutations
There are four categories of point mutations:
1. transitions (e.g., A  G, C  T)
2. transversions (e.g., T  A, C  G)
Point mutations
There are four categories of point mutations:
1. transitions (e.g., A  G, C  T)
2. transversions (e.g., T  A, C  G)
Point mutations
There are four categories of point mutations:
1. transitions (e.g., A  G, C  T)
2. transversions (e.g., T  A, C  G)
3. insertions (e.g., TTTGAC  TTTCCGAC)
Point mutations
There are four categories of point mutations:
1. transitions (e.g., A  G, C  T)
2. transversions (e.g., T  A, C  G)
3. insertions (e.g., TTTGAC  TTTCCGAC)
4. deletions (e.g., TTTGAC  TTTC)
Point mutations
There are four categories of point mutations:
1. transitions (e.g., A  G, C  T)
2. transversions (e.g., T  A, C  G)
3. insertions (e.g., TTTGAC  TTTCCGAC)
4. deletions (e.g., TTTGAC  TTTC)
• in coding regions, point mutations can involve silent
(synonymous) or replacement (nonsynonymous)
changes.
Point mutations
There are four categories of point mutations:
1. transitions (e.g., A  G, C  T)
2. transversions (e.g., T  A, C  G)
3. insertions (e.g., TTTGAC  TTTCCGAC)
4. deletions (e.g., TTTGAC  TTTC)
• in coding regions, point mutations can involve silent
(synonymous) or replacement (nonsynonymous)
changes.
• in coding regions, insertions/deletions can also cause
frameshift mutations.
Loss of function mutations in the cystic
fibrosis gene
“Copy-number” mutations
“Copy-number” mutations
• these mutations change the numbers of genetic
elements.
“Copy-number” mutations
• these mutations change the numbers of genetic
elements.
• gene duplication events create new copies of genes.
“Copy-number” mutations
• these mutations change the numbers of genetic
elements.
• gene duplication events create new copies of genes.
• one important mechanism generating duplications is
unequal crossing over.
Unequal crossing-over can generate
gene duplications
Unequal crossing-over can generate
gene duplications
Unequal crossing-over can generate
gene duplications
lethal?


neutral?
“Copy-number” mutations
• these mutations change the numbers of genetic
elements.
• gene duplication events create new copies of genes.
• one mechanism believed responsible is unequal
crossing over.
• over time, this process may lead to the development of
multi-gene families.
 and -globin gene families
Chromosome 11
Chromosome 16
Timing of expression of globin genes
Retrogenes may also be created
• retrogenes have identical exon structures to their
“progenitors” but lack introns!
Retrogenes may also be created
• retrogenes have identical exon structures to their
“progenitors” but lack introns!
Example: jingwei in Drosophila yakuba
Retrogenes may also be created
• retrogenes have identical exon structures to their
“progenitors” but lack introns!
Example: jingwei in Drosophila yakuba
Alcohol

dehydrogenase
(Adh)
Chromosome 2
Chromosome 3
Retrogenes may also be created
• retrogenes have identical exon structures to their
“progenitors” but lack introns!
Example: jingwei in Drosophila yakuba
Alcohol

dehydrogenase
(Adh)
Chromosome 2

mRNA
Chromosome 3
Retrogenes may also be created
• retrogenes have identical exon structures to their
“progenitors” but lack introns!
Example: jingwei in Drosophila yakuba
Alcohol

dehydrogenase
(Adh)

mRNA

cDNA
Chromosome 2
Chromosome 3
Retrogenes may also be created
• retrogenes have identical exon structures to their
“progenitors” but lack introns!
Example: jingwei in Drosophila yakuba
Alcohol

dehydrogenase
(Adh)

mRNA

cDNA
Chromosome 2

“jingwei”
Chromosome 3
Whole-genome data yields data on gene families
“Copy-number” mutations
• transposable elements (TEs) are common.
“Copy-number” mutations
• transposable elements (TEs) are common.
• three major classes of TEs are recognized:
“Copy-number” mutations
• transposable elements (TEs) are common.
• three major classes of TEs are recognized:
1. insertion sequences (700 – 2600 bp)
“Copy-number” mutations
• transposable elements (TEs) are common.
• three major classes of TEs are recognized:
1. insertion sequences (700 – 2600 bp)
2. transposons (2500 – 7000 bp)
“Copy-number” mutations
• transposable elements (TEs) are common.
• three major classes of TEs are recognized:
1. insertion sequences (700 – 2600 bp)
2. transposons (2500 – 7000 bp)
3. retroelements
Chromosomal inversions lock blocks of genes together
Inversions act to suppress crossing-over…
 inviable
 inviable
Inversions act to suppress crossing-over…
 inviable
 inviable
… and can lead to co-adapted gene complexes
Chromosomal inversions in
Drosophila pseudoobscura
Here is a standard/arrowhead heterozygote:
Here are more inversion heterzygotes:
Chromosomal translocations are also
common
Changes in chromosome number are
common
Changes in chromosome number are
common
• in mammals, chromosome numbers range from N = 3 to
N = 42.
Changes in chromosome number are
common
• in mammals, chromosome numbers range from N = 3 to
N = 42.
• in insects, the range is from N = 1(some ants) to N =
220 (a butterfly)
Changes in chromosome number are
common
• in mammals, chromosome numbers range from N = 3 to
N = 42.
• in insects, the range is from N = 1(some ants) to N =
220 (a butterfly)
• karyotypes can evolve rapidly!
Muntiacus reevesi
Muntiacus muntjac
Muntiacus reevesi; N = 23
Muntiacus muntjac; N = 4
Genome mutations
Genome mutations
• polyploidization events cause the entire genome to
be duplicated.
Genome mutations
• polyploidization events cause the entire genome to
be duplicated.
• polyploidy has played a major role in the evolution of
plants.
Genome mutations
• polyploidization events cause the entire genome to
be duplicated.
• polyploidy has played a major role in the evolution of
plants.
• ancient polyploidization events have also occurred in
most animal lineages.
Generation of a tetraploid
Where do new genes come from?
Where do new genes come from?
An example: the antifreeze glycoprotein (AFGP) gene
in the Antarctic fish, Dissostichus mawsoni
Where do new genes come from?
An example: the antifreeze glycoprotein (AFGP) gene
in the Antarctic fish, Dissostichus mawsoni
Reference:
Chen et al. 1997. Proc. Natl. Acad. Sci. USA 94: 3811
Where do new genes come from?
An example: the antifreeze glycoprotein (AFGP) gene
in the Antarctic fish, Dissostichus mawsoni
• antifreeze proteins allow these fishes to inhabit
subzero sea temperatures.
Where do new genes come from?
An example: the antifreeze glycoprotein (AFGP) gene
in the Antarctic fish, Dissostichus mawsoni
• antifreeze proteins allow these fishes to inhabit
subzero sea temperatures.
• act by inhibiting the growth of ice crystals.
Where do new genes come from?
An example: the antifreeze glycoprotein (AFGP) gene
in the Antarctic fish, Dissostichus mawsoni
• antifreeze proteins allow these fishes to inhabit
subzero sea temperatures.
• act by inhibiting the growth of ice crystals.
• the AFGP gene dates to ~10 – 14 million years ago
(when Antarctic ocean began to freeze over).
Where do new genes come from?
Step 1. Duplication of the pancreatic trypsinogen gene
(6 exons long).
Where do new genes come from?
Step 1. Duplication of the pancreatic trypsinogen gene
(6 exons long).
Step 2. Deletion of exons 2 – 5.
see Chen et al. 1997. Proc. Natl. Acad. Sci. USA 94: 3811
see Chen et al. 1997. Proc. Natl. Acad. Sci. USA 94: 3811
Where do new genes come from?
Step 1. Duplication of the pancreatic trypsinogen gene
(6 exons long).
Step 2. Deletion of exons 2 – 5.
Step 3. Expansion of Thr-Ala-Ala triplet 41 times at
junction of exon 1.
see Chen et al. 1997. Proc. Natl. Acad. Sci. USA 94: 3811
Where do new genes come from?
Step 1. Duplication of the pancreatic trypsinogen gene
(6 exons long).
Step 2. Deletion of exons 2 – 5.
Step 3. Expansion of Thr-Ala-Ala triplet 41 times at
junction of exon 1.
Step 4. Expression of AFGP gene in liver, release into
blood.
Convergent evolution of an AFGP gene
in the arctic cod, Boreogadus saida
Convergent evolution of an AFGP gene
in the arctic cod, Boreogadus saida
• the AFGP gene in B. saida also has a Thr-Ala-Ala
repeating motif!
Convergent evolution of an AFGP gene
in the arctic cod, Boreogadus saida
• the AFGP gene in B. saida also has a Thr-Ala-Ala
repeating motif!
• appears to have evolved independently because:
Convergent evolution of an AFGP gene
in the arctic cod, Boreogadus saida
• the AFGP gene in B. saida also has a Thr-Ala-Ala
repeating motif!
• appears to have evolved independently because:
1. flanking regions show no homology to trypsinogen
Convergent evolution of an AFGP gene
in the arctic cod, Boreogadus saida
• the AFGP gene in B. saida also has a Thr-Ala-Ala
repeating motif!
• appears to have evolved independently because:
1. flanking regions show no homology to trypsinogen
2. different number and locations of introns
Convergent evolution of an AFGP gene
in the arctic cod, Boreogadus saida
• the AFGP gene in B. saida also has a Thr-Ala-Ala
repeating motif!
• appears to have evolved independently because:
1. flanking regions show no homology to trypsinogen
2. different number and locations of introns
3. codons used in repeating unit are different