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The Case of Fur Color
Evolution in Beach Mice
or
http://www.evo-ed.com
Wouldn’t it be nice if I had white fur???
Anatomy of a Hair Follicle
• The hair shaft is
made of cornified
cells – that is, dead
cells filled with
keratin.
• Within the region of
matrix stem cells are
specialized pigmentproducing
melanocyte cells.
Melanocyte
cells
Image adapted from: http://www.nature.com/ng/journal/v38/n3/fig_tab/ng0306273_F1.html
Image: http://www.dermnetnz.org/doctors/principles/images/hair-bulb.gif
Hair Color
• Two pigments
– Eumelanin
– Pheomelanin
Melanocyte
cells
Pheomelanin
Roland Mattern
Eumelanin
Roland Mattern
Image adapted from: http://www.nature.com/ng/journal/v38/n3/fig_tab/ng0306273_F1.html
Hair Color
• Dark Hair: Lots of eumelanin
• Fair Hair: More pheomelanin, less eumelanin
• Red Hair: Lots of pheomelanin
How is melanin produced?
• Transmembrane proteins that are stimulated
by a hormone.
• When these
melanocortin
receptor proteins
are stimulated….
LOTS of
eumelanin is
produced.
•
Stimulation of MC1R
leads to lots of cAMP
production.
•
c(tyr)
cAMP leads to the
expression of at least
four genes: c(tyr),
Tyrp1, Tyrp2, p
Tyrp1
Tyrp2
p
Image from:
http://www.sciencedirect.com/science/article/pii/S0021967307010199
•
Stimulation of MC1R
leads to lots of cAMP
production.
•
c(tyr)
cAMP leads to the
expression of at least
four genes: c(tyr),
Tyrp1, Tyrp2, p
•
MC1R stimulation
leads to lots of cAMP
production which
means Tyrp1, Tyrp2
and p are expressed
lots of eumelanin.
Tyrp1
Tyrp2
p
Image from:
http://www.sciencedirect.com/science/article/pii/S0021967307010199
•
Stimulation of MC1R
leads to lots of cAMP
production.
•
cAMP leads to the
expression of at least
four genes: c(tyr),
Tyrp1, Tyrp2, p
•
Inadequate MC1R
stimulation leads to
less cAMP production
which means Tyrp1,
Tyrp2 and p are not
expressed  less
eumelanin; more
pheomelanin.
c(tyr)
Tyrp1
Tyrp2
p
Image from:
http://www.sciencedirect.com/science/article/pii/S0021967307010199
•
Stimulation of MC1R
leads to lots of cAMP
production.
•
c(tyr)
cAMP leads to the
expression of at least
four genes: c(tyr),
Tyrp1, Tyrp2, p
• MC1R is a
pretty big deal.
Tyrp1
Tyrp2
p
Image from:
http://www.sciencedirect.com/science/article/pii/S0021967307010199
Eumelanin and Pheomelanin
Images from: www.chem.sc.edu/analytical/chem107/lab4_032205.pdf
1.0
The Natural History of
Fur Color in Beach Mice
1.1
Fact Sheet:
Peromyscus polionotus
• Common names: Beach Mouse
or Old Field Mouse.
• Location: Southeastern U.S.A.
• Habitat: Sand burrows in dunes
or old fields.
• Home-range: ~1000 m2
• Breeding: Monogamous pairbonding. Litters of 2-8 pups,
every 30 days.
• Lifespan: 9-12 months.
1.2
Fur Color
Subspecies:
leucocephalus
trissyllepsis
allophrys/peninsula
ris
ammobates
subgriseus
1.3
How are populations of these sub
species distributed within the range
of the Beach Mouse?
?
?
?
?
?
1.5
The Spatial Distribution of Fur Color
Lighter colored sub-species live on light sand beaches;
darker colored sub-species live in darker habitat.
1.6
Question
Assuming that ancestral populations of beach
mice had dark brown fur, what could have
happened to explain the occurrence of lightcolored coastal sub-species?
The Melanocortin-1-Receptor (MC1R)
• What can you tell me about the MC1R protein?
– Write three things down.
The Melanocortin-1-Receptor (MC1R)
• What can you tell me about the MC1R protein?
– Write three things down.
• Do you think there are any differences between the
MC1R protein of dark haired mice and the MC1R
protein of light haired mice? If so, what?
– Write something down.
The Melanocortin-1-Receptor (MC1R)
• What can you tell me about the MC1R protein?
– Write three things down.
• Do you think there are any differences between the
MC1R protein of dark haired mice and the MC1R
protein of light haired mice? If so, what?
– Write something down.
• Do you think there are any differences between the
mc1r allele of dark haired mice and the mc1r allele of
light haired mice?
– Write something down.
4.6
Consequence of Mutation
There is a change in the the amino acid identity
at position #67: an Arginine vs. a Cysteine
Amino Acid Sequence Dark Fur:
MPTQGPQKRLLGSLNSTSTATPHLGLATNQTGPWCLQVSIPDGLFLSLGLVSLVENV
LVVIAITKNRNLHSPMYSFICCLALSDLMVSISLVLETAIILLLEAGALVTRAALVQQLD
NVIDVLICGSMVSSLCFLGVIAIDRYISIFYALRYHSIVTLPRARRAIXGIWVASIFFSTLFI
TYYNHTAVLICLVTFFLAMLALMAXLYVHMLTRAYQHAQGIAQLQKRQGSTXQGFCL
KGAXTLTIILGIFFLCWGPFFLHLTLIVLCPQHPTCSCI
FKNFNLYLVLIIFSSIVDPLIYAFRSQELRMTLREVLLCSW
Amino Acid Sequence Light Fur:
MPTQGPQKRLLGSLNSTSTATPHLGLATNQTGPWCLQVSVPDGLFLSLGLVSLVEN
VLVVIAITKNCNLHSPMYSFICCLALSDLMVSISLVLETAIILLLEAGALVTRAALVQQL
DNVIDVLICGSMVSSLCFLGVIAIDRYISIFYALRYHSIVTLPRARRAIVGIWVASIFFSTL
FITYYNHTAVLICLVTFFLAMLALMAILYVHMLTRAYQHAQGIAQLQKRQGSTRQGFC
LKGAATLTIILGIFFLCWGPFFLHLTLIVLCPQHPTCSCI
FKNFNLYLVLIIFSSIVDPLIYAFRSQELRMTLREVLLCSW
Freeman 4e Fig. 15.4
Substitution Mutation
• A single nucleotide substitution mutation in the mc1r
gene causes a change in amino acid #67 in the MC1R
protein chain.
• When amino acid #67 is cysteine, the MC1R protein is
unable to effectively bind the α-MSH. This changes the
pigment pathway and eumelanin is not produced.
mc1r Gene Sequence
Let’s look at what happens when ONE SPECIFIC nucleotide is changed….
5’-ATGCCCACCCAGGGGCCTCAGAAGAGGCTTCTGGGTTCTCTCAACTCCACCTCCACAGCC
ACCCCTCACCTTGGACTGGCCACAAACCAGACAGGGCCTTGGTGCCTGCAGGTGTCTGTC
CCGGATGGCCTCTTCCTCAGCCTGGGGCTGGTGAGTCTGGTGGAGAATGTGCTGGTCGTG
ATAGCCATCACCAAAAACCGCAACCTGCACTCGCCCATGTATTCCTTCATCTGCTGTCTG
GCCCTGTCTGACCTGATGGTGAGTATAAGCTTGGTGCTGGAGACGGCTATCATCCTGCTG
CTGGAGGCAGGGGCCCTGGTGACCCGGGCCGCTTTGGTGCAACAGCTGGACAATGTCATT
GACGTGCTCATCTGTGGCTCCATGGTGTCCAGTCTTTGCTTCCTTGGTGTCATTGCCATA
GACCGCTACATCTCCATCTTCTATGCATTACGTTATCACAGCATTGTGACGCTGCCCCGG
GCACGACGGGCCATCGTGGGCATCTGGGTGGCCAGCATCTTCTTCAGCACCCTCTTTATC
ACCTACTACAACCACACAGCCGTCCTAATCTGCCTTGTCACTTTCTTTCTAGCCATGCTG
GCCCTCATGGCAATTCTGTATGTCCACATGCTCACCCGAGCATACCAGCATGCTCAGGGG
ATTGCCCAGCTCCAGAAGAGGCAGGGCTCCACCCGCCAAGGCTTCTGCCTTAAGGGTGCT
GCCACCCTTACTATCATTCTGGGAATTTTCTTCCTGTGCTGGGGCCCCTTCTTCCTGCAT
CTCACACTCATCGTCCTCTGCCCTCAGCACCCCACCTGCAGCTGCATCTTTAAGAACTTC
AACCTCTACCTCGTTCTCATCATCTTCAGCTCCATCGTCGACCCCCTCATCTATGCTTTT
CGGAGCCAGG AGCTCCGCATGACACTCAGGGAGGTGCTGCTGTGCTCCTGGTGA- 3’
mc1r Gene Sequence
Let’s look at what happens when ONE SPECIFIC nucleotide is changed….
5’-ATGCCCACCCAGGGGCCTCAGAAGAGGCTTCTGGGTTCTCTCAACTCCACCTCCACAGCC
ACCCCTCACCTTGGACTGGCCACAAACCAGACAGGGCCTTGGTGCCTGCAGGTGTCTGTC
CCGGATGGCCTCTTCCTCAGCCTGGGGCTGGTGAGTCTGGTGGAGAATGTGCTGGTCGTG
ATAGCCATCACCAAAAACTGCAACCTGCACTCGCCCATGTATTCCTTCATCTGCTGTCTG
GCCCTGTCTGACCTGATGGTGAGTATAAGCTTGGTGCTGGAGACGGCTATCATCCTGCTG
CTGGAGGCAGGGGCCCTGGTGACCCGGGCCGCTTTGGTGCAACAGCTGGACAATGTCATT
GACGTGCTCATCTGTGGCTCCATGGTGTCCAGTCTTTGCTTCCTTGGTGTCATTGCCATA
GACCGCTACATCTCCATCTTCTATGCATTACGTTATCACAGCATTGTGACGCTGCCCCGG
GCACGACGGGCCATCGTGGGCATCTGGGTGGCCAGCATCTTCTTCAGCACCCTCTTTATC
ACCTACTACAACCACACAGCCGTCCTAATCTGCCTTGTCACTTTCTTTCTAGCCATGCTG
GCCCTCATGGCAATTCTGTATGTCCACATGCTCACCCGAGCATACCAGCATGCTCAGGGG
ATTGCCCAGCTCCAGAAGAGGCAGGGCTCCACCCGCCAAGGCTTCTGCCTTAAGGGTGCT
GCCACCCTTACTATCATTCTGGGAATTTTCTTCCTGTGCTGGGGCCCCTTCTTCCTGCAT
CTCACACTCATCGTCCTCTGCCCTCAGCACCCCACCTGCAGCTGCATCTTTAAGAACTTC
AACCTCTACCTCGTTCTCATCATCTTCAGCTCCATCGTCGACCCCCTCATCTATGCTTTT
CGGAGCCAGG AGCTCCGCATGACACTCAGGGAGGTGCTGCTGTGCTCCTGGTGA- 3’
The Cytosine at position 199 has now changed to a Thymine.
4.7
Consequence of Mutation
The specific amino acid sequence is very
important. One mutation within the sequence can
have affect how the protein interacts with the
melanocyte-stimulating hormone (α-MSH).
Amino Acid #67 = Arginine
Amino Acid #67 = Cysteine
4.9
The Role of the MC1R Protein
When amino acid #67 is cysteine, the MC1R
protein is unable to effectively bind the α-MSH.
This changes the pigment pathway and
eumelanin is not produced.
5.1
Plausible Mechanism;
Observable Pattern
• In biological research, to say that something at
the molecular or genetic level is responsible
for a phenotypic trait, a plausible mechanism
and an observable relationship should be
identified.
5.2
Mechanism: Alleles of mc1r Gene
• The mc1r gene has two alleles:
Allele R
Allele C
[Arginine at pos #67]
Codes for a functional
MC1R protein.
[Cysteine at pos #67]
Codes for a non-functional
MC1R protein.
The genetic code for these two alleles differs by a
single nucleotide substitution.
5.4
Observable Relationship:
Genes vs. Fur Color
• There are three possible genotypes associated with
the mc1r gene:
5.4
Observable Relationship:
Genes vs. Fur Color
• There are three possible genotypes associated with
the mc1r gene:
1. RR  Arginine-Arginine: Indicates that both copies of
chromosome 16 have an arginine amino acid at
position #67 of the mc1r gene. + Eumelanin
5.4
Observable Relationship:
Genes vs. Fur Color
• There are three possible genotypes associated with
the mc1r gene:
1. RR  Arginine-Arginine: Indicates that both copies of
chromosome 16 have an arginine amino acid at
position #67 of the mc1r gene. + Eumelanin
2. CC Cysteine-Cysteine: Indicates that both copies of
chromosome 16 have a cysteine amino acid at position
#67 of the mc1r gene. - Eumelanin
5.4
Observable Relationship:
Genes vs. Fur Color
• There are three possible genotypes associated with
the mc1r gene:
1. RR  Arginine-Arginine: Indicates that both copies of
chromosome 16 have an arginine amino acid at
position #67 of the mc1r gene. + Eumelanin
2. CC Cysteine-Cysteine: Indicates that both copies of
chromosome 16 have a cysteine amino acid at position
#67 of the mc1r gene. - Eumelanin
3. RC  Arginine-Cysteine: Indicates that one copy of
chromosome 16 has an arginine amino acid on
position #67 of the mc1r gene; the other copy has a
cysteine in position #67 of the mc1r gene. ? Eumelanin
5.5
Observable Relationship:
Genes vs. Fur Color
• Is there a relationship between the fur color
of beach mouse individuals and the allele
combinations (genotypes) they possess?
CC homozygous = ?
RR homozygous = ?
RC heterozygous = ?
House Mouse Karyotype (Mus musculus)
Chromosome 8 is approx. 130,000,000 bp
5.6
Observable Pattern:
Color Scoring
Ear
Rostrum
Eyebrow
Whiskers
Cheek
Ventrum
Ankle
5.7
Observable Relationship:
Scoring System
2
1
2
1
2
1
1
0
2
0
1
0
2
0
0
0
5.8
Observable Pattern:
Rostrum Color
Proportion of Individuals
1
Light (0)
0.8
Medium (1)
Dark (2)
0.6
0.4
0.2
0
RR
RC
CC
Mouse Genotype
Mice with the genotype RR have the darkest
rostrum color.
5.9a
Observable Pattern: All Body Parts
Average Color Scores for:
Body Part
Rostrum
Whisker
Cheek
Eyebrow
Ear
Ventrum
Ankle
Average
RR Individuals
2.00
1.42
1.28
1.83
1.13
0.91
1.06
RC Individuals
1.81
1.00
1.25
1.54
0.80
0.55
0.82
CC Individuals
0.81
0.45
0.69
0.79
0.28
0.00
0.29
1.38
1.11
0.47
Hoekstra et al 2006
5.9b
Average Color Scores for:
Body Part
Rostrum
Whisker
Cheek
Eyebrow
Ear
Ventrum
Ankle
Average
RR Individuals
2.00
1.42
1.28
1.83
1.13
0.91
1.06
RC Individuals
1.81
1.00
1.25
1.54
0.80
0.55
0.82
CC Individuals
0.81
0.45
0.69
0.79
0.28
0.00
0.29
1.38
1.11
0.47
Question: What does the above table tell you? Does it
confirm or refute a genetic basis for differences in fur
color among mice?
5.10
Questions:
There is a clear pattern: beach mice with the RR
genotype tend to be darker than those with the
RC or CC genotype.
1. Why is the average score for RR mice score
less than 2 for most body parts?
2. Why is the average score for CC mice greater
than 0 for most body parts?
3. RC mice are closer in fur color to RR mice
than CC mice. Does this mean that R is
dominant over C? Be prepared to explain
your answer.
5.11
Question:
Differences in fur color among beach mouse
populations can be fully explained by the
relative frequency of C and R alleles present
within each population.
1.
2.
3.
4.
5.
Strongly Agree
Agree
Unsure/Confused
Disagree
Strongly Disagree
5.12a
Predict Allele Frequencies
___% R
___% C
___% R
___% C
___% R
___% C
___% R
___% C
___% R
___% C
___% R
___% C
5.12b
Actual Allele Frequencies
100% R
0% C
30% R
70% C
70% R
30% C
5% R
95% C
95% R
5% C
100% R
0% C
5.13
Fur color differences among beach mouse subspecies (i.e. populations) cannot be fully
explained by differences in R:C allele
frequencies. Why not?
In Class Exercise on Mouse Evolution
Scenario: Start with an ancestral, inland
population in which all individuals have dark fur.
The ancestral population evolves, resulting in one
population that is still inland, and another that now
lives on the beach.
Present-day Inland
Population
Ancestral Inland
Population
Present-day Beach
Population
Time
In Class Exercise on Mouse Evolution:
Questions for Student Teams to Consider

When did the ancestral population live? How big was it (number of
individuals)?
•

How big is the present day inland population (number of
individuals)?
•

What are the mc1r genotype frequencies? The mc1r allele
frequencies?
How big is the present day beach population (number of
individuals)?
•

What were the mc1r genotype frequencies? The mc1r allele
frequencies?
What are the mc1r genotype frequencies? The mc1r allele
frequencies?
Where along the timeline did an R  C substitution in MC1R occur?
2.0
The Ecology of
Fur Color in Beach Mice
2.1
Beach Mouse Food Facts:
2.2
Hunting Style of Predators
Sight and Sound
Hunters
Taste/Smell
Hunter
2.3
Predator-Prey Experiment
(The Advantage of Fur Color)
2.4
Predator-Prey Experiment
(The Advantage of Fur Color)
• Owls catch dark mouse
first 37% of the time
• Owls catch light mouse
first 63% of the time.
• Owls catch dark mouse
first 64% of the time
• Owls catch light mouse
first 36% of the time.
2.5
Regional Pattern:
Fur Color and Habitat Color
- Researchers
examined fur color in
nine beach mouse
populations.
- Fur color brightness
was significantly
correlated to soil
brightness where
each population
lived.
2.6
Predation Study – Clay Mice
(A) Two locations with different color soil where predation on clay
mice was tested. (B) Most attacks in light soil environments were on
dark mice; most attacks in dark soil environments were on light mice.
2.6b
Attack on a Clay Mouse
2.7
Summary
• Evidence suggests
that fur color may
have evolved as a
result of selective
predation.
• Fur coloration matching the
habitat coloration leads to
less detection by predators
and increases the odds of
successful reproduction.
6.6
Clicker Q1
The C  T substitution at position
199 of the mc1r gene:
A. arose by a mutation in the beach mouse populations in
response to a need for protection from predation.
B. leads to the failure of melanocytes to make an MC1R
protein.
C. arose by a mutation then increased in frequency because
it was selectively advantageous in the beach mouse
populations.
D. had no effect on the beach mouse populations.
E. produced an alternate allele that was detrimental to mice
on the white sand beaches
6.7
Clicker Q2
What was the reason for the lighter coat colors of
the mice on the white sand beaches?
A. Owls and other carnivores prey on beach mice that do
not carry the mutant allele.
B. A substitution of cysteine for arginine at position 67
of the MC1R protein.
C. A substitution of thymine for cytosine at position 199
of the mc1r gene nucleotide sequence.
D. The failure of melanocytes to lay down melanin
pigment in the cortex of hairs of the lighter colored
beach mice.
E. The poorer binding affinity for α-MSH and the lower
amount of cAMP produced by individuals with the
mutated MC1R protein.