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Genetics: The source of
variability for evolution
How population survival strategies
determine human biology and
provides the basic background for
human variation
Diversity of form and function
• The basis of evolution is
variation
• But, where does
variability in biological
form and function come
from?
• There are two levels of
evolution we will be
interested in:
• Macro-level evolutionary
change, the appearance of
new species, and
• Micro-level evolutionary
change, the generation by
generation changes in the
genes of populations.
What does the genetic material
do, anyway?
• The genetic material has a number of important functions:
1. Transmit genetic information from one generation
to the next (humans produce human infants and not rats or
elephants).
2. Since every cell in the body (with several
exceptions) has more or less the same genetic material as
the original cell (the fertilized egg), the genetic material
must be able to reproduce itself when new cells are
produced during growth and development as well as
normal body maintenance.
3. The genetic materials are organized around a
sequence of chemical ‘bases’ that encode for the synthesis
of proteins, a huge class of chemicals that perform a wide
range of functions in the body.
What determines cell structure
and function?
• Proteins that are
expressed
• Unique expression by
cell type
• How is this
controlled?
• Look to the cell
nucleus
Chromosomes
• Carries information as part
of their structure
• Name=colored bodies
when stained and seen
microscopically
• Species-specific number
in each cell nucleus, with
the chromosome number
usually expressed in pairs
(the complexity of the
living thing is not
reflected in the
chromosome number
(chimps, for example,
have more chromosomes
than humans).
Human chromosomes
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Species specific number=46
23 pairs of chromosomes
Specifially:
22 pairs of autosomes
– or, homologous chromosomes
• 1 pair of sex chromosomes
– XX female
– XY male
• Question: Why are there pairs
of chromosomes?
Where do the chromosomes
come from?
• We are originally one
cell:
• 23 of maternal origin
– ova carry these
• 23 of paternal origin
– sperm carry these
• If every cell has 46,
how do these end up
with only 23 and why?
Meiosis
• How many of you remember the process of
meiosis well enough to explain it to your
classmates?
Meiosis
If we start out as one cell, how do
we get so big and complicated?
• BIG
=cell division
(Mitosis)
• Complicated
=cell differentiation
Mitosis
• Cell Division
• Chromosomal
Replication
Differentiation
• Unique proteins in
different cell types
Proteins: What are they?
• You are what you eat!
• Functions include:
– Structure
– Transport
– Immune
• Function reflects their
structure
– Proteins have 3
dimensional structure
– Folded chains
Proteins: Structural specifics
• Structure:
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Three dimensional
Folded chain
Polypeptide chain
of amino acids (aa)
20 common aa
• Different proteins
have different aa
sequences
Amino acids: What are they and where do they come from?
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Glycine (gly)
Glutamic acid (glu)
Alanine (ala)
Aspartic acid (asp)
Valine (val)
Isoleucine (Ile)
Leucine (leu)
Serine (ser)
Threonine (thr) Proline (pro)
Lysine (lys)
Arginine (arg)
Glutamine (gln) Aspargine (asn)
Methionine (met) Cysteine (cys)
Tryptophan(trp) Tyrosine (tyr)
Histidine (his)
Phenylalanine(phe)
• Chemical group
based on their
composition: an
“amine” and an
“acid”
• Of the 20 common
aa,
– 10 the body can
make
– 10 must be eaten
• (essential aa)
Proteins: How they are made:
1. From amino acids
• Polypeptide chains=aa
• Sequence of aa crucial
to structure, and thus
function
• Sequence determined
by series of nucleic
acids and the genetic
code
• Determined by a gene
met valhisleuthraspalaglulys
val ala ala
ss
cys
leu
trp
gly
lys
val
asn
ser
asp
glu
What is a gene?
• A “recipe” for a
protein
• Located at a specific
region (locus) on a
specific chromosome
• Implications:
– different chromosomes carry
different information
• Question:
– do homologous chromosomes
carry the same information?
A gene up-close: is a
coding sequence of DNA
• The relationship
between chromosomes
and DNA:
• Chromosomes are
packaged DNA
DNA
• Double helix structure
• Biochemically:
– Deoxyribose sugar
– Nucleic Acids
– purines:
adenine, guanine
– pyrimidines: thymine, cytosine
• Base pair rules:
c g
a t
Base pair rules illustrated:
DNA self-replication
Genes and their protein products:
How does a gene “code” for a protein?
What is the process by which the structure of
DNA determines the structure of a protein?
• For example, how is a piece of coding DNA translated?
• CCTGAGGAG
• GGACTCCTC
The genetic code
• 1. Only one strand of DNA is the ‘recipe’, or
code
• The “genetic code” :
three sequential nucleic acids specify an
amino acid
• DNA: CAAGTAGAATGCGGACTTCTT
• AA: val his leu thr pro glu glu
Code to Protein: Shuttle system
• A messenger transmits DNA sequence to
protein assembly site
– messenger RNA (Ribose Nucleic Acid)
• distinct from DNA: single strand C G A Uracil
– self-assembles as it “reads” the DNA by basepair rules
– goes to ribosome, site of protein assembly
Translate this DNA into mRNA:
•
CAAGTAGAATGCGGACTTCTT
• A.
• B.
GTTCATCTTACGCCTGAAGAA
GUUCAUCUUACGCCUGAAGAA
The genetic code: codons
• mRNA: GUUCAUCUUACGCCUGAAGAA
• GUU CAU CUU ACG CCU GAA GAA
M-RNA strand to protein
• Mirror image of DNA
• Identifies a sequence
of amino acids, and
thus a protein
• HOW Are amino acids
gathered together in
the correct sequence?
• The genetic code:
• A TRANSLATOR
molecule
• t-RNA:
3NA
m-RNA meets t-RNA:
polypeptide chain of amino acids built
• mRNA:GUUCAUCUUACGCCUGAAGAAAAG
• GUU CAU CUU ACG CCU GAA GAA AAG
caa
gua
gaa
ugc
gga
cuu
cuu
uuc
Case Study: Genetics in action at
the level of
the population
• Case study: SCA
• Background:
– 1912 James Herrick:
• Case Report
Blood smear analysis
– 1940’s family studies:
• Mendelian genetics
Proteins: Structural specifics
• Structure:
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Three dimensional
Folded chain
Polypeptide chain
of amino acids (aa)
20 common aa
• Different proteins
have different aa
sequences
Red Blood Cells:
What do they do?
• Origin in bone marrow
– 120 day life cycle
• Oxygen-carriers
– Pick up oxygen in
lungs
– Deliver oxygen to
body tissues
• By what mechanism?
Rbcsinblood on top half
alvertonoutpouch on bottom
A Protein!
Hemoglobin: Function
• In red blood cells
• Transport protein
• Carries oxygen
– How?
The function depends on structure:
How hemoglobin works
• Three dimensional
• Four components:
– Two “alpha” chains
• chromosome 16
– Two “beta” chains
• chromosome 11
• Red marks the spot!
– Where oxygen binds
– Iron ion critical here
• Hemoglobin: Structure
Sickle Cell Anemia
• Sickle Cell:
– red blood cell shape
• Anemia:
– poor oxygen delivery
• Cause:
– abnormal hemoglobin
• A genetic disease
What causes the sickling?
• Hemoglobin molecule
changes shape
• Results in distortion of
rbc
• Functional effects?
Why does the hemoglobin do this?
• WHEN: Abnormal
hemoglobin molecule
unstable under
conditions of low
oxygen, high acidity
•HOW: Crystalline
structure results
•WHY? Structural
instability
Hemoglobin “S” vs Hemoglobin “A”
(Sickle [S] vs Normal [A])
First 6 amino acids:
• Beta globin gene:
Valine
Valine
Histidine
Histidine
Leucine
Leucine
Threonine
Threonine
Proline
Proline
Glutamic acid
Valine
A
S
– 146 amino acids
• Hbs beta globin chain
– one different amino
acid
– valine replaces
glutamic acid at
position 6
One nucleic acid apart
• DNA
• HbA: GGACTTCTT
Pro
Glu
Glu
• HbS: GGACATCTT
Pro
Val
Glu
Population Frequency of HbS
• Africa
– In some places, 1 in 5
people are carriers, or
– HbS/HbA genotype, or
heterozygous
(hetero=different)
– A co-dominant trait:
both proteins are expressed
Heterozygote vs
Homozygote?
Dominant
vs recessive?
Review:
• At each locus, there are two
genes; they are either the same
or different. This illustrates
allelic variability
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Homozygote
Heterozygote
Dominant
Recessive
HbS and adaptation:
• In a population of 100 individuals, calculate
the number of HbS and HbA genes if 20 %
of the people are heterozygotic and the rest
are homozygotic normal.
• What is the percentage of HbS and HbA
genes in the population?
• Why do you think there are no HbS/HbS
individuals?
Genes vs genotype
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In 100 individuals
genotype
genes
20 are HbS/HbA = 20 HbS + 20 HbA
80 are HbA/HbA =
160 HbA
20 HbS
180 HbA
20/200 = 10% HbS and 180/200=90% HbA
Why is the frequency of HbS
high in some populations?
Malaria
• Disease caused by:
• Mosquito-borne
• Parasite
– Plasmodium
• Illness:
– fever
– rigor
– sweats
• High mortality
– very high in infants
and children
• Who survives?
Malarial Illness and Parasite
• Illness intensity
related to parasite
density
– Fewer parasites, less ill
• Mechanisms to
decrease parasites:
– kill mosquitoes (DDT)
– interrupt parasite
lifecycle (anti-malarial
drugs)
– change the microenvironment of the
parasite in the body
• parasite needs oxygen
How to make the body inhospitable for the
parasite and increase the likelihood of
individual human’s survival
• Decrease available
oxygen to parasite
• Within limits set by
the survivability of the
host
• Red blood cell
biochemistry
Malaria in Africa
• Symptoms:
– fever, rigor, sweats
• Disease organism:
Parasite: Plasmodium
falciparum
gambia
vivax
malariae
• Vector: Mosquito
– Anopheles gambiae vs
– Anopheles funestus
Natural Selection and the introduction of a new
agricultural technique
• Anopheles funestus populations
• The possibility for parasite-human contact
• People contract malaria, & high mortality
follows
• Who survives?
Mutants
• Individuals with traits that are adaptive in the face
of parasites:
• In central Africa, HbS/HbA individuals:
• Parasites use host oxygen, causing conditions
resulting in sickling of red blood cells
• Anemia is detrimental to parasite survival
• Parasite numbers decrease, individual improves
An example of natural selection
Malaria-Sickle Cell Anemia
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In summary:
Human cultural behavior (agriculture)
Ecosystem change
Malaria
Selection for originally rare mutation in hemoglobin: selection favored
the heterozygote
Specifically, “balanced selection” occurred:
1. People with normal hemoglobin (HbA/HbA) died of malaria
2. People with only abnormal hemoglobin (HbS/HbS) died of anemia
3. Individuals with HbS/HbA genotype lived to reproduce
This is an example of differential reproduction/differential mortality
Many solutions to the malaria
problem
• In Southeast Asia, the disease thalassemia
represents a similar outcome of selection for
hemoglobin variants
• In the Mediterranean, other red blood cell
enzyme errors
• The heterozygote had the advantage
To consider:
• How is it possible that there are these
diverse solutions to the same problem?
• How would you expect the gene frequency
of the HbS gene in the United States today
to compare with what it was two centuries
ago?
Many ways to make the body
inhospitable to the parasite
Red blood cell biochemistry
Populations gene pools: unique and adaptive
• Reflect reproductive success in local
environments
• Small, isolated populations
• Different random mutations may become
successful by chance
• This reflects genetic drift
How are new genes introduced
into populations?
• By people!
• Migration into and out of populations:
people take their genes with them
• This is an example of gene flow
• For example, the relative frequency of HbS
in the populations of African descent in the
United States has decreased in the past two
centuries as a result of intermixture with
other populations.
Concepts you should know and understand after our
discussions:
I. Basic Genetics
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The differences between chromosomes, gene, allele
How cell division occurs
Meiosis
DNA, RNA and the process of protein synthesis
How mutations, recombination, translocation effect this
Codon
The relationship between nucleic acid, amino acid, protein
The human karyotype: autosomes, sex chromosomes
Concepts you should know and understand after our
discussions: II. How genetics works in populations
• The specific case of sickle cell anemia:
– An example of a mutation that became advantageous to a
population
– The specifics of the mutation, the structure and function of
hemoglobin, how it affects the red blood cell, and the effects for
the individual
• The selective pressure of malaria:
– The nature of the disease, the organism that causes it, how it is
contracted by people; how they survive it.
• Why did malaria and sickle cell anemia evolve together in a human
population?
– An example of balanced selection
• How genetic mutation, natural selection, genetic drift and gene flow
effect a population’s gene pool
Genetics and the evolution of
human diversity