BIOE 109Summer 2009

Lecture 4- Part IMutation and genetic variation

1. Mutation

2. Gene Flow

3. Genetic drift

4. Natural selection

Four basic processes that can explain evolutionary changes:

Sources of genetic variation

1. Crossing over during meiosis- creates new combinations of alleles on individual chromosomes

2. Independent assortment- creates new combinationschromosomes 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 combinationschromosomes 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.  

Chromosome 11

Chromosome 16

and -globin gene families

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

Alcoholdehydrogenase(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

Alcoholdehydrogenase(Adh)

Chromosome 2 Chromosome 3

mRNA

Retrogenes may also be created  

• retrogenes have identical exon structures to their “progenitors” but lack introns! 

Example: jingwei in Drosophila yakuba

Alcoholdehydrogenase(Adh)

Chromosome 2 Chromosome 3

mRNA

cDNA

Retrogenes may also be created  

• retrogenes have identical exon structures to their “progenitors” but lack introns! 

Example: jingwei in Drosophila yakuba

Alcoholdehydrogenase(Adh)

Chromosome 2 Chromosome 3

mRNA

cDNA “jingwei”

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…

… and can lead to co-adapted gene complexes

inviable

inviable

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