Download Heredity,Gene Expression, and the

Heredity,Gene Expression, and the
'Central Dogma'
Ch 9: Patterns of Inheritance
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Gregor Mendel (1822-1884)
Mendel's Insights into
Inheritance (p. 146):
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Simple, powerful experiments
with garden peas (see p. 146):
Cross-fertilized peas with
contrasting traits
Mathematics to interpret
results.
1866 paper: Parents pass
discrete 'heritable factors'
(genes) responsible for traits
to offspring.
Terms Used in Genetics: (P. 149)
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Gene
Locus (pl. loci)
Diploid cells: 2 copies of each gene.
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pairs of homologous chromosomes
Haploid cells: 1 copy of each gene
Allele: A certain version of a gene.
Homozygous: 2 copies of same allele.
Heterozygous: 2 different alleles
Genetics Terms
Illustrated (p. 149)
More Genetics Terms (p.148-149)
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Dominant allele: Expressed when present
(uppercase symbol “U”).
Recessive allele: Masked by dominant allele
(lowercase symbol “u”)
Genotype: Individual’s actual genes (DNA).
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genotype symbols:
● homozygous dominant (AA)
● homozygous recessive (aa)
Phenotype: Appearance, traits of individual.
Generation terms: P= parental, F1= first, F2 =
second.
Mendel's Experiments (p. 148-152)
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Monohybrid cross (observed only 1 trait); p. 148:
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Crossed white flowered plants (homozygous recessive)
with purple
(homozygous dominants).
F1 offspring: all purple-flowered (dominant).
F2 offspring: 3:1 ratio (purple to white)
Contradicted prevailing “blending” theories of the
time.
Monohybrid Cross:
Flower Color in Garden Peas (p. 149)
P
F1
X
pp
PP
Pp
p
P
P
F1
PP
Pp
F2
Pp X Pp
p
Pp
pp
See the punnett-square method of showing genetic possibilities (p. 148)
Mendel’s Theory (law) of Segregation:
(p. 147-149)
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Diploid Individuals (2n) have 2 copies of
each gene:
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(pairs of homologous chromosomes).
Gene-pairs separate (segregate) during
reproduction (meiosis); p. 148.
Thus, a sperm or egg only caries one copy
of a given gene.
Testcross -- Supports Segregation: (P. 152)
Dominant trait, unknown genotype:
a) If homozygous: All offspring dominant.
b) If heterozygous: 1:1 ratio.
a)
X
pp
PP
b)
Pp X pp
p
p
P
Pp
Pp
p
pp
pp
Experiments with 2 Traits: Dihybrid
Crosses (P. 150)
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Crossed dominant for 2 traits with recessive for 2
traits:
Our example –seed color & shape—book uses
flower color & plant height.
F1: Dominant (heterozygous) for both.
F2: 9:3:3:1 ratio of phenotypes:
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Expected ratio if each gene pair assorted into gametes
independently of the other.
Dihybrid Cross: Seed Color & Shape
(See p. 150)
P
Wrinkled green
Round yellow
rryy
RRYY
x
Gametes
RrYy
F1
RY
F2
Gametes
4 possibilities
ry
RY
RY
Ry
rY
ry
Ry
x RrYy
rY
ry
Mendel’s Theory (law) of Independent
Assortment (p. 150-151):
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Each pair of genes is sorted into gametes
independently of other gene pairs.
Exception:
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Genes located close together on the same
chromosome.
such genes are linked (p.163).
Crossing over disrupts linkage: Distant genes still
assort independently.
Possible Allele Combinations &
Genetic Diversity
1 gene pair (monohybrid cross) – 3 genotypes.
2 gene pairs – 9 possible genotypes.
10 gene pairs – Nearly 60,000 genotypes
20 gene pairs – Nearly 3.5 Billion genotypes
We have thousands of gene pairs!!!
More Patterns than Mendel Thought:
Variations on Mendel's Themes (p. 158-161)
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Linkage (p. 163).
Incomplete dominance (p. 158).
Codominance: A,B,O blood types (p. 159).
Pleiotropy: Multiple effects of a single gene (p. 160).
Multiple genes affect a trait (polygenic inheritance);
p. 161.
Traits due to environmental rather than genetic
effects (p. 161).
Chromosomes & Human Genetics
The human Genome (p. 130 in ch. 8):
● 46 chromosomes.
● 23 pairs.
● Approx. 3.2 billion base pairs (1n)
Autosomes and Sex Chromosomes
(p. 130 in Ch 8)
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Autosomes -- Ordinary chromosomes
(homologues exactly alike)
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22 pairs of autosomes
Sex chromosomes:
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Homologues not always alike (X is not like Y)
Determine gender (p. 131).
● XX (both alike) in females
● XY in males.
X
Y
The 46 Human Chromosomes (p. 130)
Autosomes
Sex
Chromosomes
Human Sex Inheritance
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Female produces eggs with only X.
Male produces sperm:
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1/2 X
1/2 Y
eggs
x
x
x
xx
xx
Girls
y
xy
xy
Boys
xy x xx
sperm
Human Inheritance Patterns: Autosomal
Dominant Inheritance (p. 156)
Eggs from normal mother
a
a
A
Aa
Aa
Affected
a
aa
aa
Normal
Aa x aa
Sperm from
affected father
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Achondroplasia: A type of dwarfism
Huntington disease: Progressive brain
deterioration after age 30.
Polydactyly: Extra fingers, toes.
Human Inheritance: Autosomal Recessive
Inheritance (p. 154-155)
Eggs from carrier mother
A
A
AA
a
Aa
a
Aa
Normal
Aa x Aa
Sperm from carrier father
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Albinism:
Tay Sach disease.
Cystic fibrosis.
Sickle-cell disease.
PKU (phenylketonuriea).
Normal
aa
Affected
X -Linked Recessive Inheritance:
(p. 165-166):
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Females not affected as often as males: May be masked by
dominant allele on other X.
Son can’t inherit from father.
Carrier mother
Color blindness (p. 165).
Xx
Hemophilia (p. 166).
Normal father
xy
Meiosis &
Gamete formation
x
y
X
x
xx
xx
Carrier
Normal
Xy
xy
Affected
Normal
Meiosis &
Gamete
formation
Girls
Boys
Chapter 10: DNA Structure & Function
(P. 172)
The Discovery of DNA (p 175, in part)
• 1868: J.F. Miescher isolated “nuclein” (DNA) from cell nucleii.
• 1944: Oswald Avery— Hereditary substance in Streptococcus cell
extracts was DNA
• 1950’s: Hershey & Chase—DNA hereditary substance in
bacteriophages (viruses).
• 1949: Erwin Chargaff— A=T, C=G.
• 1951: Rosalind Franklin—Preliminary findings on DNA structure.
• 1953: Watson & Crick develop model for DNA structure.
Characteristics of DNA (P. 174-176)
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DNA: Polymer of nucleotides:
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(Nucleotide = 5-carbon sugar—deoxyribose-- +
phosphate + base)
Four nucleotide bases (p. 175):
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Adenine (A)
Guanine (G)
Thymine (T)
Cytosine (C)
Structure of DNA (p. 176)
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2 strands, antiparallel.
Strands connected by complementary base
pairing:
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Adenine always pairs with Thymine
Guanine always pairs with Cytosine
The strands twist: “double helix”.
The Central Dogma of Molecular Biology
The normal “Molecular chain of Command” (p. 178)
First proposed by Francis Crick
DNA: Encoded
information.
RNA: Information
from DNA; carried to
ribosomes to make
proteins.
Proteins: Provide
structure & help carry
out almost all
biological activity.
Replication: Passing DNA information
to New Cells During Division (P. 177):
1) The 2 DNA strands unwind, unzip.
2) Complimentary pairing of new nucleotides.
3) Second strands form (enzyme: DNA
polymerase).
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“Semiconservative”: Half of new molecule conserved
from original.
4) Proofreading & repair enzymes fix errors.
Semiconservative DNA Replication
(p. 177)
T
DNA
Polymerase
T
C
T
C
T
C
T
C
C
New strands form
by complementary
base pairing
C
T
G
A
C
T
A
G
C
T
C
T
RNA: Ribonucleic Acid
Transmits DNA instructions to ribosomes for protein
synthesis: (P.178-179)
● DNA transcription RNA translation Protein
Nucleotides with ribose rather than deoxyribose:
● Single strand.
Four bases:
● Uracil (instead of Thymine)
● A, G, and C (like DNA)
Three Types of RNA (p. 182-183)
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Messenger RNA = mRNA
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Ribosomal RNA = rRNA
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encoded genetic message (protein code).
Codon: consecutive 3-base sequence (each
represents 1 amino acid); p. 179.
Part of ribosomes.
Transfer RNA = tRNA (p. 183)
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Brings amino acids to ribosome.
Anticodon on tRNA pairs with codon of mRNA.
The Genetic Code: A Code for Proteins
(p. 180)
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Codons: 3-base “words”
Universal genetic Code (Figure 10.11, p. 180)
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Each codon codes for an amino acid.
● Often several codons for the same amino acid.
● “degenerate code”.
“Stop” codon -- ends protein synthesis process.
Universal: same for all life forms!
The Universal Genetic Code (p. 180)
First Base
C
A
G
}
}
}
}
}
}
}
G
UGU
UGC }Cys
UGA }Stop
UGG }Trp
CGU
CGC
CGA Arg
CGG
AGU
AGC }Ser
AGA
AGG }Arg
GGU
GGC
GGA Gly
GGG
}
}
U
C
A
G
U
C
A
G
U
C
A
G
U
C
A
G
Third Base
U
U
UUU
UUC }Phe
UUA }Leu
UUG
CUU
CUC
CUA Leu
CUG
AUU
AUC Ile
AUA Met/
AUG- Start
GUU
GUC
GUA Val
GUG
Second Base
C
A
UCU
UAU
UCC
UAC }Tyr
UCA Ser
UAA
UCG
UAG }Stop
CCU
CAU
CCC
CAC }His
CCA Pro
CAA }Gln
CCG
CAG
ACU
AAU
ACC
AAC }Asn
ACA Thr
AAA
ACG
AAG }Lys
GCU
GAU
GCC
GAC }Asp
GCA Ala
GAA
GCG
GAG }Glu
Protein Synthesis Process
1) Transcription: mRNA Copied From DNA
(p. 181-182)
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DNA “unzips”, one DNA strand a template for
mRNA.
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Complementary base pairing with DNA
Enzyme: RNA polymerase.
mRNA is “edited” & processed (p.182) efore
leaving nucleus.
Transcription (p. 181)
RNA Polymerase
Template DNA strand
mRNA
2) Translation: mRNA to Protein
(p. 184-185)
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All 3 types of RNA involved:
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rRNA :
tRNA
mRNA:
Translation process:
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Initiation (p. 184):
● Ribosome & mRNA assemble on “start codon”
Elongation: tRNA brings amino acids to ribosome as it
“reads” codons on mRNA (p. 184).
Translation (p. 184-185)
Amino acid
Growing
Polypeptide
LYS
LYS
LEU
GLU
ALA
G C
A
Ribosome
Anticodon
mRNA
{
C
A G A A G C U
ARG
tRNA
AA G C G
T U
Codon
3) Termination (p. 184):
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Ribosome encounters a “Stop” codon:
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“UAA” UGA, or “UAG”.
Ribosome disassembles.
mRNA released.
New protein released.
Mutations: Ultimate Source of genetic
Variability (p. 186-187)
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Any change in DNA nucleotide sequence.
Can involve as little as 1-base pair or large DNA regions.
Types:
● Base substitutions (no effect, or change an amino acid).
● Deletions
● Insertions
Duplication/ loss of whole chromosomes or chromosme sets.
● Down syndrome: extra copy of chromosome 21.
While sometimes harmful, Nature's raw material for evolution
(p. 187).
Causes: DNA replication errors, radiation, certain chemicals.
Controls over Genes
(Chapter 11)
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Most Eukaryotic cells use fraction of their genes
(5-10%) at any time (p. 200):
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Gene regulation: turning genes on / off programs
differentiation.
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Genetically identical cells develop into different cell
types w/ different structures & functions.
Differentiation.
Selective expression of genes.
Cancers (p. 199) often associated with genes
that encode (defective) proteins used to regulate
other genes.
Gene Regulation in Prokaryotic Cells
( p. 200)
An example of prokaryotic Gene control.
Operon: a series of genes consisting of:
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Regulator gene -- codes for a repressor protein.
Promoter -where RNA polymerase binds.
Operator -where repressor binds.
Structural genes: for 1 or more enzymes etc.
Regulator
Operator
RNA
Gene 1 Gene 2
Polymerase
Gene 3
Repressor
Promoter
Transcription & protein synthesis
Promoter
RNA
Polymerase
Repressor
Off
ON
Eukaryotic Gene Regulation
(p. 202, 303)
More complex than for prokaryotes
Regulation occurs at multiple points during
gene expression process (Fig. 11.3, p. 202):
● Regulation of DNA packing
● Regulation of transcription
● Enhancer or activator proteins
● Silencer (repressor) proteins
● RNA processing
● Splicing: Remove non-coding “introns”
● Alternative splicings for same gene.
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Regulating RNA breakdown
Regulation of Translation
Protein activation & breakdown
Eukaryotic Gene Regulation
(continued; p. 203-204)
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Regulation of DNA packing
Regulation of transcription
RNA processing
RNA breakdown (control of an
mRNA's lifetime)
Regulation of Translation:
● Regulatory proteins block/allow
translation
Protein activation
Timing of protein breakdown
Cell signaling (p. 205)
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Multicellular organisms:
Certain cells produce
chemicals (hormones)
that effect gene
regulation in other cells.
Cancer: Regulation Gone Wrong
(p. 211-214)
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“Oncogene” --any gene (mutant) that causes cancer.
Proto-oncogene: a normal gene with potential to be an
oncogene.
● Many code for growth factors & other proteins that
stimulate or regulate cell cycle.
● Tumor suppressing genes: when normal, slow &
control cell growth & division.
DNA Mutation of these genes may result in loss of control
over cell cycle.
Multiple mutations required for a full-fledged cancer cell:
● Cell cycle stuck 'on'
● Cells lose ability to recognize neighbors & stay in own
tissue (metastasis).
Cloning (p. 207-209)
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Can a cell be “de-differentiated and stimulated to
develop into a new organism?.
Common in plants:
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Rooting cuttings.
Tissue culture from a single cell relatively easy.
Natural asexual reproduction.
Some animals (salamanders, invertebrates)
regenerate lost parts.
Difficult in mammals:
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Process usually involves exchanging an egg nucleus
with nucleus of desired clone.
Egg's regulatory environment “fools” nucleus into
becoming a zygote nucleus.
Chapter 12: DNA Technology
Recombinant DNA technology, Genetic Engineering, &
Biotechnology
Tools of Rcombinant DNA Technology (p. 222-224):
● Restriction enzymes (p. 224):
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Derived from certain bacteria.
Cut DNA only at specific base sequences.
Many restriction enzymes now known.
Some produce staggered cuts (“sticky ends”:
Any DNA fragments cut by same enzyme can join &
form Recombinant DNA (p. 220).
DNA fragments from different sources can Join.
Restriction Enzymes & Recombinant
DNA (P. 224)
1) Restriction enzyme
cuts DNA
GATGTCGACA
CTACAGCTGT
2) DNA fragments with “sticky ends”
GTACTGATGT
CATGACTACAGC
3) DNA fragment from another
organism
CGACA
TGT
CGACACCTAT
TGTGGATA
4) Recombinant DNA
GTACTGATGT CGACACCTAT
CATGACTACAGC TGTGGATA
Plasmids & Bacteria (p. 222)
Small “extra” circular DNA molecules.
Not basic genes but may provide useful traits
(antibiotic resistance).
● Many bacteria can share plasmid copies
(conjugation).
●
Plasmids
Main DNA
Using Plasmids as Vectors to Insert foreign
DNA into Bacteria (p. 223)
1) Cut out desired genes
(restriction enzyme).
2) Cut plasmid
(same enzyme).
+
3) Mix plasmid &
foreign fragments.
4) Recombinant
plasmids.
Bacterial colonies
Transformed colonies
5) Expose bacteria to recombinant plasmids: May take them up.
6) Screen bacterial colony for transformed individuals:
7) Transformed bacterial colonies synthesize desired protein.
PCR to Rapidly Copy DNA (p. 227)
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Polymerase Chain Reaction:
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Mixture of:
● DNA sample.
● Nucleotides
● Special heat-resistant DNA Polymerase
● Primers.
Repeatedly heat (separate strands) & cool (allow
base pairing & polymerization).
DNA doubles with each cycle.
Can obtain enough DNA from tiny sample:
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Single hair, blood stain.
Gel Electrophoresis to Detect &
Compare DNA Samples (p. 226-229)
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Cut DNA with restriction enzymes.
Place on gel & subject to electric current.
DNA migrates toward + pole.
Smaller pieces migrate faster.
Compare patterns among samples
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Blood from murder scene vs. other blood samples
One application: “DNA profiling ( “DNA
fingerprinting”); P. 226-227.
Gel Ectrophoresis to Detect &
Compare DNA Samples:
Who is the Murderer?
DNA Sequencing
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Methods to determine exact nucleotide
sequences of short pieces of DNA.
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Automated sequencing machines.
Human Genome Project (P. 230).
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Overlapping pieces used to determine longer sequences.
Developed sequence for all human chromosomes.
Other important sequenced genomes (P. 230): Rat,
yeast, infuenza bacterium, rice, chimpanzee, &
more.
Applications of Biotechnology
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Produce drugs (Example insulin) -often via genes inserted into
bacteria (p. 220-221).
Crime forensics (p. 226).
Investigate parentage (p. 226).
Improve crops: disease resistance or pesticide resistance (p. 221).
Gene therapy (insert genes to correct nonfunctional ones) .
“Pharm” animals that produce human-use proteins or healthier fats,
etc. (p. 222).
Environmental cleanup: engineered bacteria that digest toxic waste.
Genomics: develop records of complete genomes of organisms
(p. 230).
●
Proteomics: systematic study of full protein sets of organisms. (p.
233)
The End
Version 13.02