Genetics: The source of variability for evolution

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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

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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.

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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.

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What determines cell structure and function?

• Proteins that are expressed
• Unique expression by cell type
• How is this controlled?
• Look to the cell nucleus

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Chromosomes

• Carries information as part of their structure
• Namecolored 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).

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Human chromosomes

• Species specific number46
• 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?

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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?

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Meiosis

• How many of you remember the process of meiosis
  well enough to explain it to your classmates?

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Meiosis
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If we start out as one cell, how do we get so big
and complicated?

• BIG
• cell division
• (Mitosis)
• Complicated
• cell differentiation

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Mitosis

• Cell Division
• Chromosomal Replication

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Differentiation

• Unique proteins in different cell types

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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

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Proteins Structural specifics

• Structure
• Three dimensional
• Folded chain
• Polypeptide chain
• of amino acids (aa)
• 20 common aa
• Different proteins have different aa sequences

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Amino acids What are they and where do they come
from?

• 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)

• 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)

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Proteins How they are made 1. From amino acids

• Polypeptide chainsaa
• 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
val
his
leu
thr
asp
ala
glu
lys
ala
ala
val
ss
cys
leu
trp
gly
lys
val
asn
ser
asp
glu
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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?

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A gene up-close is a coding sequence of DNA

• The relationship between chromosomes and DNA
• Chromosomes are packaged DNA

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DNA

• Double helix structure
• Biochemically
• Deoxyribose sugar
• Nucleic Acids
• purines adenine, guanine
• pyrimidines thymine, cytosine
• Base pair rules
• c g
• a t

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Base pair rules illustrated DNA self-replication
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Genes and their protein productsHow 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

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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

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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 base-pair
  rules
• goes to ribosome, site of protein assembly

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Translate this DNA into mRNA

• CAAGTAGAATGCGGACTTCTT
• A. GTTCATCTTACGCCTGAAGAA
• B. GUUCAUCUUACGCCUGAAGAA

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The genetic code codons

• mRNA GUUCAUCUUACGCCUGAAGAA
• GUU CAU CUU ACG CCU GAA GAA

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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

Amino Acid
3NA

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m-RNA meets t-RNApolypeptide chain of amino
acids built

• mRNAGUUCAUCUUACGCCUGAAGAAAAG
• GUU CAU CUU ACG CCU GAA GAA AAG

caa
gua
gaa
ugc
gga
cuu
cuu
uuc






leu
thr
pro
lys
val
his
glu
glu
Beta Globin (146 aa)
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Case Study Genetics in action at the level of
the population

• Case study SCA
• Background
• 1912 James Herrick
• Case Report
• Blood smear analysis
• 1940s family studies
• Mendelian genetics

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Proteins Structural specifics

• Structure
• Three dimensional
• Folded chain
• Polypeptide chain
• of amino acids (aa)
• 20 common aa
• Different proteins have different aa sequences

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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
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A Protein!Hemoglobin Function

• In red blood cells
• Transport protein
• Carries oxygen
• How?

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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

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Sickle Cell Anemia

• Sickle Cell
• red blood cell shape
• Anemia
• poor oxygen delivery
• Cause
• abnormal hemoglobin
• A genetic disease

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What causes the sickling?

• Hemoglobin molecule changes shape
• Results in distortion of rbc
• Functional effects?

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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

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Hemoglobin S vs Hemoglobin A(Sickle S vs
Normal A)

• First 6 amino acids

• Beta globin gene
• 146 amino acids
• Hbs beta globin chain
• one different amino acid
• valine replaces glutamic acid at position 6

Valine
Valine
Histidine
Histidine
Leucine
Leucine
Threonine
Threonine
Proline
Proline
Glutamic acid
Valine
A
S
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One nucleic acid apart

• DNA
• HbA GGACTTCTT
• HbS GGACATCTT

Genetic
Pro
Glu
Glu
Mutation
Pro
Val
Glu
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Population Frequency of HbS

Heterozygote vs Homozygote?

• Africa
• In some places, 1 in 5 people are carriers, or
• HbS/HbA genotype, or heterozygous
  (heterodifferent)
• A co-dominant trait
• both proteins are expressed

Dominant vs recessive?
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Review

• At each locus, there are two genes they are
  either the same or different. This illustrates
  allelic variability
• Homozygote
• Heterozygote
• Dominant
• Recessive

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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?

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Genes vs genotype

• 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 180/20090 HbA

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Why is the frequency of HbS high in some
populations?
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Malaria

• Disease caused by
• Mosquito-borne
• Parasite
• Plasmodium

• Illness
• fever
• rigor
• sweats
• High mortality
• very high in infants and children
• Who survives?

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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 micro-environment of the parasite in
  the body
• parasite needs oxygen

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How to make the body inhospitable for the
parasite and increase the likelihood of
individual humans survival

• Decrease available oxygen to parasite
• Within limits set by the survivability of the
  host
• Red blood cell biochemistry

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Malaria in Africa

• Symptoms
• fever, rigor, sweats
• Disease organism
• Parasite Plasmodium falciparum
• gambia
• vivax
• malariae
• Vector Mosquito
• Anopheles gambiae vs
• Anopheles funestus

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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?

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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

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An example of natural selection
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Malaria-Sickle Cell Anemia

• 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

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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

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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?

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Many ways to make the body inhospitable to the
parasite

• Red blood cell biochemistry

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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

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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.

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Concepts you should know and understand after our
discussions I. Basic Genetics

• 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

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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 populations gene
  pool

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Genetics and the evolution of human diversity