Monday, 23 November 2020

What is this?
Fish and Parasitic isopod
 Monday, 23 November 2020
• Announcements
– Grades posted
– Questions and
responses posted
later today
– No office hours
Wednesday
Mean = 71.3
Median = 75
Range = 24 - 104
3
 Friday, 20 November 2020
• Review
– Mendelian genetics
• Multiple loci
– Independent assortment
• Codominance/incomplete
dominance
– Relationship genotype
to phenotype
• Replication
– Mutation
– Genetic code
 From genotype to phenotype
• Learning objectives
– What is the relationship between genotype and
phenotype?
– What is the difference between simple and
complex traits?
We’ve talked about replication,
so what’s next?
• A bunch of other things
have to happen for genes
to be expressed
• Transcription
– mRNA generated in the
nucleus
– processed
– Transported to cytoplasm
where ribosomes await
• Translation
– Proteins synthesized on
ribosomes
 Is this the end of the story?
• No

• Proteins must be processed such that they can be folded

into appropriate functional structures
– Sliced
– Sugar added
– Phosphate added 7
 Hemoglobin
• Proteins are then
assembled into
functional molecules
• Example
• Hemoglobin is a
tetramer (four subunits)
– Two copies of the A
protein
– Two copies of the B
protein
Hemoglobin molecule
• Heme (includes iron)
‒ Necessary for binding
oxygen 8
How does this complexity relate
to our discussion of genotype
and phenotype?
• Is it possible to have things with
genetically identical hemoglobin but they
appear (are phenotypically) different?
– Yes
• How?
– Differences at other genes may effect
expression
– Environmental influence
9
How does this complexity relate
to our discussion of genotype
and phenotype?
• Is it possible to have things with different
hemoglobin alleles that appear to be (are
phenotypically) the same?
– Yes
– Gene expression effects
– Dominance
– Environmental influence

10
 Why is hemoglobin important?

Oxygen

Hemoglobin holds
four oxygen
molecules to take
to different parts
of the body

11
 Relating genotype to phenotype: sickle
cell anemia
Slides modified from http://www.emory.edu/PEDS/SICKLE/

• What is sickle cell

anemia?
• An inherited disease of
red blood cells
– predominantly found in
people of African
ancestry
• Affects hemoglobin
inside the red blood
cells
12
 Sickle cell affects hemoglobin
proteins
• Sickle cell allele results from a point mutation
that changes a single amino acid in the
hemoglobin B gene
– AA normal
– AS both normal and
sickled hemoglobin
– SS sickled
hemoglobin only
– Can appear
codominant at level
of hemoglobin 13
What is Sickle Cell Disease?
AMINO ACID #6
GAA GUA
GLU VAL

This one change causes

hemoglobin to form long
strings when it lets loose
of its' oxygen. This causes
the red cell to become
deformed into a "sickle"
shape.

14
 Relating genotype to phenotype: sickle
cell anemia
• Sickle-shaped red
cells interrupt
blood flow by
blocking small
blood vessels
• Tissue that has no
blood flow is
damaged and
causes pain

15
 Diagnosis - Blood Smear

Normal

Heterozygote

Sickle red cells 16

Sickle cell anemia is prevalent in
certain locations
• Red areas: sickle cell

• Blue areas: malaria

• Purple areas: overlap

17
 Enter the mosquito
• In central Africa sickle cell
anemia is more common
• This area is infested with
malaria, transmitted by
mosquito bites
– Malaria is caused by a sporozoan
parasite that lives in RBCs

• Incomplete dominance in Africa (3 functional phenotypes)

 Sickle cell and dominance
• Different in the US
– People with AS genotypes
have enough functional
red blood cells that they
do not suffer the severe
effects of sickle cell Ryan Clark
– Unless at high altitude

• At whole individual level, A allele seems to be

dominant in the US
– Heterozygous individuals appear to be “normal”
 Beyond Mendel
• Therefore, it is important to consider
circumstances under which genetic
variation occurs
• Often a single gene has many phenotypic
effects
– pleiotropy

20
 Pleiotropic effects of
sickle cell anemia (SS individuals)
• Enlarged spleen
• Shortage of red blood
cells or anemia
• Pain episodes
• Stroke or brain damage
• Kidney failure
• Pneumonia
• Increased infections
Are all negative genetic diseases
recessive?
• No, negative mutations don’t have to be
recessive
– The process of mutation is random, regardless
of its effect on fitness
• But dominant lethals that show up before
reproduction get wiped out of population
• Why do they persist then?
– They can express trait after reproduction (late
onset - like Huntington’s disease we discussed
earlier)
22
 Do all mutations have negative
effects?
• No
• Synonymous mutations do not cause a
change in phenotype
• Impact of mutation is context dependent
– Sickle cell anemia
• Africa vs. North America

23
 Monogenic vs. Polygenic traits
• Monogenic trait:
– determined by a single gene locus
– A diploid individual can carry at most two
different alleles (one on each member of a
homologous pair of chromosomes)

• Polygenic trait:
– determined by multiple gene loci
– An individual’s phenotype is determined by
numerous alleles on several different
chromosomes
24
 Monogenic vs. Polygenic traits
• Mendel’s laws were mostly applied to
monogenic traits: traits fall into distinct
categories

• Traits we’ve studied so far are monogenic

(although blood type has more than two
possible alleles, each individual only carries
two alleles for blood type)

25
 Polygenic traits
• Many traits do not fall
into distinct
categories, and are
instead continuously
distributed
• A continuous
distribution of
phenotypes is an
indication of polygenic Example: height*
inheritance
*80% genetically
determined, ~ 700 genes
 Why continuous
distribution?
• Example - skin
pigmentation
• Three genes
– A,B,C add melanin
– a,b,c no melanin
• 7 possible phenotypes
• The more genes involved,
the more potential overlap
between phenotypes
27
 Is this the whole story?

• Is there anything else that might

contribute to phenotype?
• Let’s think about pigmentation
• There is environmental influence on
phenotypes
• Think about tanning booths...

28
Environment can make a difference!

Why might this happen? 29

 Example: PKU (phenylkeptonuria)
and the environment
• Substitution of tryptophan
for arginine (GUA for GAA)
at nucleotide 408 in the
gene
• People that are pp have a
non-functional form of the
enzyme that normally
converts phenylalanine to
tyrosine
• Excess phenylalanine is
toxic
30
 PKU effects
• This alteration of the phenylalanine
pathway affects multiple traits
(pleiotropic)
• Excess phenylalanine affects the nervous
system during development
– severe brain damage
– small head size
• It also affects production of melanin
– person is light skinned
• And the production of thyroxine
– poor thyroid function

31
 The effect of environment
• The fetus is protected
by the Pp mother
(carrier) in utero
(recessive trait)
• The mother has
functional enzymes
for converting
phenylalanine so the
fetus does not have
buildups

32
 In the right environment, PKU does not
negatively affect the child
• So, newborns are checked after birth at the
hospital for PKU
• PKU kids are fed a phenylalanine free diet
during brain growth (childhood)
pp adults with normal phenotypes!

Thus, phenotype depends on genotype and

environment

33
 Where do we go from here?
• We have:
– Discussed how animals
have dealt with the
challenges presented by
the environment, resulting
in differences among them
– Discussed how these
differences are transmitted
to future generations
• What are the processes
that generated this
diversity? 34
 Evolution and Populations
• Learning objectives
– How is Mendelian inheritance important to
populations?
– What processes affect patterns of variation
within and among populations?

35
What do Mendel’s Laws have to do with
populations?

36
 Mendel’s Laws in Populations
• What does this have to do with evolution
(e.g., creation of biodiversity)? Think about:
– Mendel’s Law of Segregation
• For each pair of alleles, there is a 50% chance of a
specific allele ending up in a gamete
• AND
– Random mating in a population
• If mating is random, the frequency with which
individuals mate (and thus gametes combine to form
offspring) is also a matter of probability
• Therefore, can use a Punnett square to track
reproduction at the population level 37
 Mendelian inheritance in
populations
• We have 1000
snapdragons, 640 red
(RR), 320 pink (RW), and
40 white (WW)
– Three genotypes (provided
above)
– Two alleles (R and W)
• We can quantify the
frequency of these alleles
and genotypes 38
 What is an allele frequency?
• The proportion of some specific allele in a
population
• General equations – red and white alleles
– Frequency of red allele
2*# RR  # RW Simply counting the
p( R)  number of red alleles.
2 * total # individuals
two for each RR and one
for RW.
WW allele
– Frequency 2of*#white # RW
q(W ) 
2 * total # individuals
p  q 1
 Example
• We have 1000 snapdragons, 640 red (RR),
320 pink (RW), and 40 white (WW)
• What is the frequency of red alleles?
2*# RR  # RW
p( R) 
2 * total # individuals
(2 * 640)  320
p( R) 
2000
p ( R )  0.80
• What is frequency of white alleles?
q (W )  1  p
q (W )  1  0.8  0.2
40
What is the observed genotypic
frequency?
• The proportion of a specific genotype seen
in a population
• Example for snapdragons
# red individuals 640
x(red )    0.64
total # individuals 1000
# pink individuals 320
y ( pink )    0.32
total # individuals 1000
# white individuals 40
z ( white)    0.04
total # individuals 1000
 Random mating
• Segregation of alleles Gametes males
(R and W) and random From: R W
mating means that
females RW
probability of different RR
R
genotypes is solely
determined by allele
W RW WW
frequencies (p, q)

42
 Random mating
• Segregation of alleles Gametes males
(R and W) and random R p W q
From:
mating means that
probability of different females RR
RR RW
genotypes is solely p R p × p = p 2
p×q
determined by allele W RW WW
frequencies (p, q) q q×p q × q = q2
• From these we can
predict frequency of
offspring

43
 Random mating
Gametes males
From: R p W q

females RR RW
p R p × p = p2 p×q
W RW WW
q q×p q × q = q2

• If mating is random we expect the offspring to have

genotypic frequencies of:
(p + q)[from females] × (p + q)[from males] = 1
= p2 + 2pq + q2 = 1
 Random mating
• So what does this Gametes males
mean for our R(p) 0.8 W(q) 0.2
From:
snapdragons?
• Recall R = 0.8; W = 0.2 females RR RW
0.8 R(p) p × p = 0.64 p × q = 0.16
• If mating is completely
random, we expect W(q) RW WW
genotypic frequencies 0.2 p × q = 0.16 q × q = 0.04
of offspring to be:
‒ RR = 0.64
‒ RW = 0.32 Note that these are the
‒ WW = 0.04 same as the parents!
 Hardy-Weinberg equilibrium
• Under these conditions
the population is in
equilibrium

Frequency of A
• So what do I mean by
equilibrium?
– Equilibrium means that
allele and genotype
frequencies do not Generation
change over time under
ideal conditions