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Introduction to Genetics
Why study genetics?

Revision
Double Helix

- Understanding/detection/treatment of inherited

- B-form of DNA is double helix consisting of 2

-

- Hydrogen bridges between A-T (2 bonds) & G-C

disorders
DNA forensics
Evolutionary studies: population movements
GM crops
Genealogical studies
Gene regulation, developmental studies

DNA

- Chromosome - Discrete unit of genome carrying
many genes
...

Structural Gene - Gene that encodes any RNA
or polypeptide product other than a regular
...

Sequences of daughter strands are determined
by complementary bases
...


- Bacterial transformation provided first support
- During transformation, genetic properties can be

- Replication is undertaken by a complex of

-

-

-

transferred from 1 strain to another by extracting
DNA & adding it to the 2nd
...

Phage infection showed DNA is genetic material
of viruses
...


Polymerases

-

Genetic Material of Eukaryotic Cells

- DNA can be used to introduce new genetic traits
into animal cells or whole animals
...

Denaturation -Separation of 2 strands due to
breaking of hydrogen bonds between bases
...

DNA Polymerase - Enzyme that synthesise DNA
Nucleases - Enzymes that degrade nucleic acids
- DNases & RNases categorised as
endonucleases or exonucleases
...

- Central Dogma - Information cannot be

of new genetic markers by incorporation of
added dan
In some viruses the material is RNA

Polynucleotide Chains
- Nucleoside consists of purine or pyrimidine base
linked to 1’ carbon of pentose sugar
...

- Nucleotide consists of nucleoside linked to
phosphate group on either 5’ or 3’ carbon of
(deoxy)ribose
...

- Successive (deoxy)ribose residues of
polynucleotide chain are joined by phosphate
group between 3’ carbon of 1 sugar & the 5’
carbon of the next
- 1 end of the chain (written on left) has free 5’
end & the other has a free 3’ end
Supercoiling

- Coiling of closed duplex DNA in space so it
crosses over its own axis

- Circular or linear DNA which ends are anchored
& not free to rotate

- Linking number (L) = Twists (T) + Writhe (W)

genomes of RNA
...

Translation of RNA into protein is undirectional

Nucleic Acids Hybrid by Base Pairing

- Heating causes 2 strands of DNA duplex to
separate
...


- Complementary single strands can renature or
anneal
...


Mutations

- Changes in sequence of DNA
- Occur spontaneously or induced by mutagens
- Point mutation changes single base pair
...

- True Reversion - Mutation that restores original
sequence of DNA
...

- Suppression - Mutation in 2nd gene bypasses
effect of mutation in 1st gene
...

- Can result from high frequency of change in
copy number of short, repeated sequence

- DNA Polymerase I - Replaces RNA nucleotides

- Forward mutations alter function of gene & back

DNA REPLICATION

- Before cells divide, DNA must be copied
- Watson & Crick (1953) - Semi-conservative
replication

Replication in Procaryotes
1
...

2
...

3
...

4
...

5
...

- Leading Strand: Synthesis 5’➞3’
- Lagging Strand: Synthesis in ‘wrong direction’;
Okazaki Fragments
6
...
DNA polymerase I removes RNA primers (5’➞3’
nuclease activity) replaces with DNA
nucleotides
8
...

Summary:
- Replication occurs at a replication bubble & is
bidirectional
- Occurs continuously on lagging strand (Okazaki
fragments)
- Enzymes: helicases, topoisomerases, DNA
primes, DNA polymerase & DNA ligase
...
coli DNA polymerase III makes an error 1/10
nucleotides
...

- Helicase - Unwinds
- Topoisomerase (gyrase) - Releases tension
- Primase - Makes short RNA primer

2nd strand
with DNA

- DNA Ligase - Joins up breaks in 2nd strand
Replication in Eukaryotes

- Bigger genome, replication slower
- Several replication forks active simultaneously
on each chromosome

- Replication bubbles fuse with one another
5’ Terminus Problem:

- Nothing upstream to act as a primer
- Short stretch will not be replicated &
chromosome will get shorter

- Telomerase extends lagging strand
GENES ENCODE RNAS & POLYPEPTIDES

- Allele - 1 of several alternative forms of gene
occupying given locus on chromosome
...


Genes Encode Polypeptides

- 1 gene : 1 enzyme hypothesis summarises basis
-

of modern genetics: gene is stretch of DNA
encoding 1+ isoforms of single peptide chain
Heteromultimer - Molecular complex (protein)
composed of different subunits
...

Some genes encode structural or regulatory
RNAs
...


Mutations in Same Gene

- Complementation Test - Determines whether 2
mutations are alleles of same gene
...


- Determine whether wild-type phenotype can be
produced
...


- Cistron - Genetic unit defined by

complementation test; equivalent to a gene
...

- Dominant mutations result from gain of function
...

- Silent Mutations - Mo phenotypic effect - Base
doesn’t change sequence or amount of
polypeptide or change in polypeptide sequence
has no effect
...


Introduction to Genetics
Locus May have:
Different Mutant Alleles:
- Existence of multiple alleles allows possibility of
heterozygotes that represent any pairwise
combination of alleles
...

Genetic Code

- Acridines - Mutagens that act on DNA to cause
-

insertion or deletion of single base pair
...

Combinations of mutations together insert or
delete 3 bases (multiples or 3) insert or delete
amino acids, but do not change reading of
triplets beyond last site of mutation
...

- Open Reading Frame (ORF) - Sequence of DNA
consisting of triplets that can be translated into
amino acids starting with initiation codon &
ending with termination codon
...

- Unidentified Reading Frame (URF) - Open
reading frame with an undetermined function
...


- Gene is collinear with its mRNA & polypeptide
products
...

Gene Expression - Process which information in
a sequence of DNA in a gene is used to produce
RNA or polypeptide, involving transcription &
translation
Each mRNA consists of untranslated 5’ region, a
coding region & an untranslated 3’ UTR or trailer
In eukaryotes, gene may contain introns not
represented in polypeptide product
...

RNA Processing - Modifications to RNA
transcripts of genes
...

Pre-mRNA - Nuclear transcript that is processed
by modification & splicing to give mRNA
...

Ribosome - Large assembly of RNA & proteins
that synthesises polypeptides under direction
from mRNA template
...


- Transfer RNA (tRNA) - Intermediate in
-

polypeptide synthesis that interprets genetic
code
...

A tRNA has an anticodon sequence that is
complementary to a triplet codon representing
the amino acid
...

They are not expressed as RNA or polypeptide
& affect only contiguous stretch of DNA
...


- Production of 2 identical daughter cells
...

No complex machinery for nucleoid separation
...


- Multicellular forms common: extensive tissue

development
Cell Cycle:
M (mitosis) ➞ G1 (gap 1) ➞ G0 (cells that ceased
division) ➞ S Phase (DNA synthesis) ➞ G2 (gap 2)
- Interphase (G1, S & G2)
- Before mitosis chromosomes are duplicated (S)
- Cycle must be regulated so events occur with
right timing, in right order & once per cycle
...

Cell Cycle Control by Cytoplasmic Proteins:

- Cyclins & Cyclin-dependent kinases (Cdks)
- Cdks add phosphate groups to protein
substrates, activating/inactivating them
...


Introduction to Genetics

- Levels of cyclins fluctuate during different
phases of cycle

Stages of Mitosis:
- (Interphase)
- Prophase
- (Prometaphase)
- Metaphase
- Anaphase
- Telophase
Prophase:
- Longest phase, chromosomes condense &
become visible
...
May pass to other pole, or attach to
chromosomes at centromere
Metaphase:
- Microtubules of spindle attach to each
chromosome at kinetochore (attached to
centromere)
- Chromosomes pulled along spindle to align at
equator
...


Revision
2)
3)
4)
5)

Transferred pollen from stamen of white flower
to carpel of purple flower
Pollinated carpel matured into pod
Planted seeds from pod
Examined offspring: all purple flowers

Mendel’s First Law

- Each observable trait is determined by a pair of
physical factors
...

- When individual inherits 2 different forms of a
trait, one is dominant over the other (recessive)
...


- Locus - Chromosomal location of a gene
...


- Heterozygous - Copies of 2 different alleles of a
particular gene
...

- Phenotype - Observable expression of
genotype
...


- Initially thought genes were diluted by 50%
- Demonstrated patterns of inheritance
- Suggested existence of physical units of
inheritance (genes)

- Showed that genetic traits are discontinuous
Why peas?

- Cheap, easy to propagate, short reproductive
cycle

- Large number of sees
- Controlled breeding assured
- Recognisable traits

Process:
1) Removed stamens from purple flower

other & parent cells
Consequence of Meiosis

Introduction to Genetics

Revision

- Reduction in chromosome number from diploid
to haploid e
...
46 to 23 in humans

- Cycles of meiosis & fusion (at fertilisation)
-

result in normal diploid number being
maintained- Essential for sexual reproduction
...

Events of meiosis explain segregation &
independent assortment of genes described in
Mendel’s laws
...


- Hold mRNA & tRNA in correct position for

- Charged tRNA corresponding to next triplet on
mRNA is added at A site
...

- 1st tRNA is released from amino acid, & leaves
ribosome, which moves along by 1 triplet so 2nd
tRNA occupies P site
...

- Elongation continues until STOP codon is
encountered (UAG, UAA, UGA)
...

Anticodons
- At least one type of tRNA for each amino acid
...

- Once 1st part of mRNA has passed through

translation to occur
...


- Message carried by mRNA is read at ribosome,

& converted into series of amino acids
...

- Charging of tRNA is ATP-dependent & carried
out ammoniacal tRNA synthetases, each
specific for 1 amino acid
...

Sequence in procaryotes is AGGAGG (Shine
Dalgarno sequence)
...

Large ribosomal subunit joins & initiation
complex is complete
...

tRNA carrying methionine is brought in line with
P site on large subunit of ribosome
...


Elongation

-

ribosome, it is free to associate with another &
begin translation again
...


Proteins Undergo Modification

- Proteolysis - Initial methionine residue is
removed

- Glycosylation - Carbohydrate side-chains added
to produce glycoproteins
...
Other amino
acids may be modified by methylation
...

64(43) possible combinations
Read continuously, with no commas or overlaps
...


-

of repeated ‘A’ nucleotides in template DNA,
resulting in corresponding number of ‘U’
nucleotides
...
Rhodependent terminator sequences are rich in C &
G residues
...

mRNA is released, RNA polymerase & Rho
dissociate from DNA & transcription is complete
...


Initiation

- Only last 1 has termination sequence, so single

- RNA polymerase attaches to DNA at specific
promoter sequence
...


continuous mRNA produced, encoding several
proteins (polycistronic RNA)
Eukaryotic mRNA is monocystronic

- Promoter tells RNA polymerase where

-

- Promoters vary in efficiency of binding
...


Elongation

along template, separating DNA strands as it
goes
- Short sequence of DNA is ‘melted’ & RNA
polymerase starts to build an RNA chain in 5’➞3’
direction complementary to template strand
...

- Transcription bubble is small & re-closes after
RNA polymerase has passed
...

Termination
- Occurs when RNA polymerase encounters a
particular DNA sequence with twofold symmetry
...


Transcription in Eucaryotes
eucaryotes
...

Several other sequences further upstream
influence efficiency of binding of enzyme
including CAAt box (-75) & GC box (-90) (Low
efficiency without these)
General transcription factors (GTFs) involved in
initiation of transcription - Bind to promoter along
with RNA polymerase I
...

- Pre-mRNA must be modified before it can
undergo translation & migrate
Not Continuous:
- Most genes contain regions that don’t code for
amino acids (introns) & must be removed by a
process of mRNA splicing
- Introns (intervening sequences)
- Exons (expressed sequences)

Revision

- Variation due to gene size, nucleotide content,
-

number of introns, frequency or repetitive
elements
...


- Germline Mutations - Occur in germline cells
-

may be transmitted to all cells of next
generation
...


Types

- Point Mutations - Affects a single base pair
- Substitution (Silent Mutation)
- Neutral Mutations: Change in a sequence but no
-

effect on protein function
Substitution (Nonsense Mutation)
Single Base Deletion (Frameshift Mutation)
Three Base Deletion
Sense Mutation - STOP Codon ➞ Amino Acid
Codon

- Effect of mutation on phenotype of an organism
Removal of Introns
- Complexes of protein & nuclear RNA called
small nuclear ribonucleoprotein particles
(snRPs) recognise & bind to consensus
sequences at intron/exon boundary
...

- Intron is spliced out by action of snRPs
...

- Capping protects mRNA & essential for
ribosome binding in initiation of translation
...
Has no DNA
template & is important for efficient transport of
mRNA from nucleus & mRNA stability
...

Editing involves substitution of 1 nucleotide for
another or insertion/deletion of nucleotides
...

In eucaryotes, mRNA must pass from nucleus to
cytoplasm before translation takes place, so
mRNA always fully transcribed before translation
commences
...

Any change in DNA sequence of an organism
...

Spontaneous mutation occur in humans at a rate
of between 10-4 & 4x10-6 per gene per
generation
...

Point & nonsense mutations are more likely than
substitutions to have an effect on phenotype
...


Effects of Mutations on Phenotype

- Morphological Traits e
...
seed shape, flower

colour in Mendel’s peas, wing length & eye
colour in Drosophila
- Biochemical Variation e
...
bacteria, inability to
synthesise amino acid or vitamin
...

- Lethal Mutations - Often affecting key metabolic
enzymes, whose effects are so severe organism
is unable to survive
...
g
...

BEYOND MENDEL
Extensions of Mendel’s Principles

- 3:1 & 9:3:3:1 ratios not obtained with some traits
- All Mendel’s traits showed complete dominance

Introduction to Genetics

Revision

- Incomplete (Partial) Dominance e
...
Pink

flowers - Heterozygote phenotype is distinct
from & intermediate between two parents
- Parental phenotypes restored in F2 generation
Codominance
- 2 alleles at a locus produce a distinct phenotypic
product, both are expressed together in
heterozygotes e
...
Blood groups in humans
Causes:
- Dominance depends on how an allele is
expressed
...

- Abnormality in gene can have many phenotypic
manifestations
...
g
...

- ABO blood groups depend on expression of 1 (A
or B), both (AB) or neither (O) of 2
carbohydrates on surface of red blood cells
...
(IA & IB are
codominant)
- IA = N-acetyl-galactosamine
- IB = galactose
- Some individuals with IA or IB do not express the
A or B phenotype & appear to be Type O
(‘Bombay Phenotype’)
- Homozygous recessive for an unrelated allele
(hh) - prevents expression of A or B antigen Recessive epistasis
Lethal Alleles Disrupt Processes Essential to Life

- e
...
Yellow coat in mice causing death:
- The yellow allele is pleiotropic – affects
several traits
...


Two Genes May Affect Same Trait

- R (dominant) produces red pigment, rr no
pigments

- C (dominant) leads to breakdown of chlorophyl,

- e
...
Manx cat:
- ML allele interferes with spinal development:
- One copy: absence of tail
- Two copies: severe abnormality, embryo dies
- Products of certain genes are essential for
survival, e
...
central metabolic enzymes
...


cc allows chlorophyll to remain

Polygenic Inheritance

- Traits such as height, weight & skin colour & eye
-

-

colour are governed by several genes Continuous variation
Epistasis (Intergenic interaction) - When a gene
affects phenotypic expression of another gene
e
...

Recesive Epistasis e
...
ee marks expression of
B or b (Yellow colour produced by pigment
encoded by 3rd gene)
Dominant Epistasis - One gene will suppress
expression of another gene
- Phenotypic Ratio Gives a Clue to the Type of
Interaction

Ratio

A_B

A_bb

aaB_

aabb

Why is it difficult to study human inheritance?
Long generation time (20+yr)
Small number of offspring
Planned breeding experiments not possible
Studies based on family pedigrees

-

- Incomplete Penetrance - Expected phenotype
not produced from a particular genotype
...

May be caused by other genes or by
environmental factors
...
Only one copy
of either dominant gene is
required to make product
...


Introduction to Genetics
3:1 & 9:3:3:1 ratios seen in monohybrid & dihybrid
crosses depend on:
- Alleles being clearly dominant or recessive
- Independent assortment
- Random fertilisation
Chance Deviation - Determines exact values
obtained
Sample size is important
e
...
50% chance of a coin being heads, 50% tails
- Chance of heads always occurring: (½)n (n =
number of spins)
- e
...
(½)3 = 1 in 8 & (½)20 = ~ 1 in a million
Sum rule states probability of mutually exclusive
events occurring is sum of probabilities of individual
events
...


- 0
...

Three Characters - Trihybrid Cross

Revision
Gene Regulation in Procaryotes

- Constitutive Enzymes - Made all the time
- Inducible Enzymes - Produced when needed
- Regulatory Gene - Gene encoding for protein
-

involved in regulation of gene expression e
...

repressor
Structural Gene - Gene encoding for RNA or a
protein required for enzymatic or structural
functions

lac Operon: an Inducible Operon

- Jacob & Monod 1961: Lactose utilisation in E
...


- Lactose ➞ (β-Galactosidase) ➞ Galactose +

Glucose
Transport & Breakdown of lactose:
- Lactose Permease - Transports lactose into cell
- β-Galactosidase - Splits lactose into glucose
- β-Galactosidase Transacetylase - Function not
known
...

- Genes for all proteins found to be clustered
together as an operon (lacZ, lacY & lacA)
- Encoded as single, continuos molecule of mRNA
- ‘all or nothing’ production
...

- Use phenotypic ratio for each character
...


- Overlaps with promoter, binding of repressor

GENE REGULATION

- Not all genes are expressed all of the time
- Damaging for the cell
2 ways to control a metabolic pathway:
1) End product inhibits enzyme 1
2) End product blocks gene transcription

prevents access of RNA polymerase to promoter
in absence of lactose
...
Binds to
repressor so it can no longer attach to operator
- In presence of normal substrate (lactose) lac
operon switched on - Transcription of genes
process (allolactose binds to repressor)
- When levels of lactose fall, less allolactose to
bind to repressor, so it attaches to promoter &
inhibits lac operon transcription

Introduction to Genetics

Revision

Other Factors:

- If glucose is plentiful, no need for E
...

Amount of cAMP is regulated by concentration
of glucose
CAP binding & transcription of lac operon is also
regulated by concentration of glucose
...


Nucleus ➞ Transcription ➞ Processing: Capping 5’ poled
at 3’, RNA splicing, Compartmentalisation & Regulation
➞ Translation

Controlled Transcription of DNA

- Eukaryote:
- Intracellular signalling & intercellular

- 5 structural gene encoding enzymes involved in

tryptophan synthesis
- When tryptophan absent, transcription of operon
proceeds unhindered
...

- When tryptophan is abundant, transcription of
trp operon can be reduced 70-fold
...

- Causes premature termination of transcription:
proportion of full length to truncated transcripts
is related to amount of tryptophan present
...

- trpL contains attenuator region with 4 GC-rich
sequences with complementarity, allowing
secondary structures to form
...

Tryptophan Absent
- Region 1 contains 2 trip codons (UGG), but not
translated because no trp-tRNA available
...

- Region 1 now covered by ribosome, 2 & 3 form
alternative hairpin structure (‘anti-terminator’)
- Prevents formation of terminator (3 & 4),
transcription continues
...

Leads to termination of transcription
No transcription of structural genes
In Bacillus subtilise, attenuation is the sole
method of regualating the trp operon
...


-

communication important for transcriptional
regulation in eukaryotes
- Positive & negative regulate proteins called
transcription factors bind to specific regions of
DNA & stimulate or inhibit transcription
...
g
...
g
...


Regulation of Gene Expression by Steroid Hormones

Revision
DNA Sequences that Control Transcription

- Basal Transcription Factors - Proteins bind to
-

specific DNA sequences within promoter to
facilitate RNA polymerase alignment
...
May be upstream, downstream, or
within an intron
...

- Activators - Proteins that recognise specific
short DNA sequences inducing the efficiency of
promoters
...

- Co-activators - Protein required for a more
efficient transcription
...
Connect
activators to basal factors
...
Act on local
structure of gene
...

- Proteins are brought into contact with one
another by mediator complex
...

Activation of Transcription by Hormones
- Steroid hormone/cytosolic receptor complex
binds to HRE sequence to stimulate
transcription
- For peptide hormones, receptor stays at cell
membrane; signal is conveyed through
cytoplasm by other protein, causing transcription
factor to bind to regulatory sequence near gene
Molecular Control of Transcription in Eukaryotes

- Transcription of eukaryotic genes regulated by

interactions between proteins & DNA sequences
within or near genes
...


- mir transcript forms stem-loop structure that is

processed by enzymes Drosha & Dicer to form
miRNA
...

- Long double-stranded RNA that is transfected or
injected into a cell can be process to form an
siRNA
...

Gene Expression & Chromatic Organisation

- Various aspects of chromatin organisation
influence the transcription of genes
...

Small RNSa interfere with expression of target
mRNAs
...


Position-Effect Variegation: Change in the position
of the interaction of DNA/histones may move the
conversion of eu- to hetero-chromatin
Reverse Remodelling

- Active chromatin can be made inactive by
biochemical modifications to histones
...


- Histone methyl transferases (HMTs) add
methyl groups to histone proteins
...


Euchromatin & Heterochromatin

- Heterochromatin stains deeply
...

- Euchromatin contains the majority of eukaryotic
genes
...

- Interacts with Histones
Types of Heterochromatin
- Centric heterochromatin is located around
centromeres
- Intercalary heterochromatin is dispersed
throughout eukaryotic chromosomes
...

DNA Methylation

- Most methylated cytosines are found in

dinucleotide sequence CG, denoted mCpG
...


Introduction to Genetics

Revision

-

CpG Islands

- CpG dinucleotides occur less often than

-

expected in mammalian genomes, probably due
to mutation into TpG dinucleotides over course
of evolution
...

Most CpG islands located near transcription
start sites; cytosines in these regions rarely
methylated

Epigenetics
- 3 generations exposed to environment
- Epigenetic change is only proven if present in 4th
generation
Methylated DNA is Associated with Transcriptional
Repression
- Inactive X chromosome in female mammals is
extensively methylated
...

- Proteins that repress transcription have been
shown to bind to methylated DNA
...


POPULATION GENETICS: HARDY WEINBERG
EQUILIBRIUM

- Gene frequencies can be high or low no matter

-

Human Genome Project
- $ 3,000,000,000 public projec
- 3,3000,000,000 base pairs
- 20,500 genes
- Benefits:
- Genetic screening
- Gene identified for scientists
Post Genomic Era

- Sequencing of organism is relatively easy &
-

cheap
Human genome sequence is approaching $1000
per genome (Jan 2014)
Illumina HiSeq X Ten- 10 machines to sequence
20,000 genomes per year

Synthetic Biology

- Graig Venter 15 years & $40,000,000 to

synthesize genome of bacterial parasite (2010)

- Last week 2014: Design & production of fully
-

functional yeast chromosome
50,000 base pairs out of 250,000 were deleted,
inserted or changed
...

Introns & transposons removed
Engineering approach to biology:
- Genetics is the core tool for synthetic
biologists

how the allele is expressed, & can change,
depending on the conditions that exist
...

Hardy-Weinberg Principle provides a baseline to
determine whether or not gene frequencies have
changed in a population & whether evolution has
occurred
...
elegans
(1998)
- Flowering plant, Arabidopsis thaliana (2000)
- Human (1990 – 2003)

Synthetic DNA
Synthetic cells
Genome editing
Genetic circuits

offspring genotype frequencies can be
predicted from the parent allele frequencies
...
g
...
g
...


Mechanisms for evolutionary change:

- Mutations:
- The origin of genetic variation
- A chance process contributing to divergence
between population

- Most mutation are harmful
- Mutation rates usually very low, estimates in
human of 1 in 100 million bp

- How many mutations in each new zygote?
- Types of mutation: Point, Frameshift,
Insertion, Deletion etc
...
g
...
g
...
S allele at frequency 10% in parts of
Africa
...

alleles increase - Natural selection
phenotype is called it’s fitness
...
g
...


A classic example of natural selection:

- Peppered moth (Biston betularia)
- Bernard Kettlewell’s Experiments in 1950s
- Mark-recapture experiments in polluted &
unpolluted woods

What are the constraints on evolution?

- Natural selection cannot act upon an ell that
doesn’t exist

- Two solutions to same problem:
- Blue spotted ray
- Peacock flounder
Trade Offs Constrain Evolution:

- All adaptions impose fitness costs & benefits
- e
...
Large size & weaponry in males in
polygynous species

How have humans influenced evolution?
Pest control
Disease control
Inadvertent e
...
sport hunting
Moment of organisms around the globe
Genetically modified organisms
Climate change

-

DNA, where is its replaced

immune system crashes
Positive Selection fro Resistance to HIV
- Chemokinereceptor CCR5 helps HIV entry into
cells
- Some people have a 32 base pair deletion of
CCR5, 32
- Δ32 allele results in a non-functioning protein
- A study of 1955 at high risk of HIV infection
- No Δ32 homozygotes were HIV positive
Selection & Evolution of the HIV Virus
- Reverse transcription is error prone therefore
HIV has a very hugh mutation rate
- Generation time: 2
...

These rapidly evolve to evade host immune
defences
...

- Among people who were HIV positive those with
the Δ32 allele developed AIDS later than those
without it
- 10 years after infection:
- 48 % of +/+ people were AIDS free
- 70% of +/ Δ32 people were AIDS free
Selection & Evolution of the HIV Virus
- Reverse transcription is error prone therefore
HIV has a very high mutation rate
- Generation time: 2
...

- Rapidly evolve to evade host immune defences
- In one patient studied, 7 years after infection no
virus has the original genotype

Introduction to Genetics
HIV & evolution of Drug Resistance

- HIV will become resistant to drugs quickly due

Revision

- MHC Diversity (Genomic compatibility) -

- If behaviour improves an individual’s chance of

e
...
Using smell female sticklebacks select
males with high MHC class II diversity
...
g
...
e
...
Sticklebacks,
male colour is genetically correlated with
female preference for that colour
...
e
...
Female
preference in African widowbird, tails often
more than half metre long
Sensory Bias:
- Females selecting on basis of sensory pleasure
- e
...
Tundra frog “chucks”
...
e
...
Orange spot
on guppies (sign of health?)

-

- Sexual selection is strongest in species where

to:

- High mutation rate
- Quick generation time
- High recombination rate
SEXUAL SELECTION

- The component of natural selection represented
by success in mating

- About reproductive success, not survival
- Risk is worth it
How Sexual Selection Works

-

mating, it will be selected for even if it decrease
survival
Will develop until improvements balanced by
fitness costs, response will stop
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
001 nucleotide
substitutions per year
Comparison of substitution rates within &
between genes can give valuable insights into
mechanisms involved
If rates are similar between several species,
substitution rates can give insights into dates of
evolutionary events

gliding squirrels

-

Whiptail lizards

Different parts of genes evolve at different rates:

- Males
- Genomic imprinting in mammals
- Triploid asexual species do evolve e
...

MOLECULAR EVOLUTION

-

Molecular level of DNA & protein sequences
Natural selection acts on individual
Populations & genes change over time
Longer time frames than population genetics

Nucleotide Substitutions in DNA Sequences
- Homologous Proteins - Protein in different
species that share a common ancestor
- An amino acid is most likely to be replaced by
another amino acid with similar characteristics
2 Evolutionary Principles:
1) Mutation are rare events
2) Most dramatic alteration removed from gene
pool by natural selection

Sequence

Nucleotide substitutions per
site per year (x10-9)

Functional Genes:

- 5’ flanking region
- Coding sequence,

2
...
65

- Intron
- 3’ flanking region

synonymous

0
...
70
4
...
85

- Coding sequence, non

- Pseudogenes: Inactivated versions of genes that
are no longer functionally constrained

- Mutation rate will be same
- Substitution rates are different

Introduction to Genetics
Codon Usage Bias

- Illustrates effect of even tiny difference in fitness
when subject to natural selection

- Synonymous substitutions not completely
-

neutral
Some triplet codons favoured over others
e
...
Lacuna specified by ix different codons but:
- 60% of leucine codons in E
...
g
...
g
...
g
...
g
...
g
...
g
...

Phylogenetic trees: Tree of life
- Originally 3 major groups: animals, plants &
protists
- Became 5 kingdoms (prokaryotes, protista,
plants, fungi & animals

in intensity of natural selection at each locus

- Histones - Positively charged, essential DNA
binding proteins

- Slow evolving
- Apolipoproteins - Non specifically carried, wide
variety of lipids in blood of vertebrate

Rates of Evolution in Mitochondrial DNA

- Mammalian mitochondria genome - Circular,
tDNA, ~15,000bp long

- Humans - 1/10,000 size of nuclear genomes, 2
rRNAs, 22 tRNAs, 13 proteins
- Exceptionally high substitution rate:
- Synonymous - 5
...
g
...
1

Birds

113

1
...
3

Amphibians

2

0
...
1

Invertebrates

98
384

Mean Number
of Alleles

Heterozygosity

Status

1
...
10

0
...
23

Endangered

(1829-94)
Seychelles
Kestrel

1
...
12

European
Kestrel

5
...
68

South African
Rook Kestrel

5
...
63

Species
Mauritius Kestrel

- Restored
- Museum

0
...
00026
- Heterozygosity in southern = 0
...
g
...
2

Threatened Species (IUCN), Why?

- Anthropogenic activity: Farming, logging, mining,

Not
Endangered

damming, building
...

- Hunting, fishing, trading
...


- Common outcome: Reduce population size
Conservation Genetics

- Habitat destruction causes populations to
become geographically isolated

- Studies consequences of small population size:
- Genetic drift
- Inbreeding
- Bottlenecks
What happens to genetic variation in small
populations?
- Genetic Drift - The loss of genetic variation by
chance
- Faster in small populations

Effect on Population Variability
1) Population go extinct before genetic factors
come into play
2) Genetic factors are important
Genetic Variation & Extinction Risk

- Data from other species
- The World Conservation Union lists all
endangered species as:

- Critically endangered
- Endangered
- Vulnerable

- Recent Study: Compared genetic variation in
-

threatened species & taxonomically close nonthreatened species
Null Hypothesis: If genetic effect unimportant
then little difference between threatened & nonthreatened species

Introduction to Genetics

- Alternative: If genetic potential is reduced in

threatened species they should have lower
heterozygosity in >50% of paired comparisons

Inbreeding
- Loss of genetic variation is threat to small
population
- 2nd threat is inbreeding - Mating between close
relatives
- Small population = Fewer potential mates
- Probability of mating with relative immerses
- Effect: Increase homozygosity in inbred
individuals
- Inbred individuals are more likely to:
- Carry 2 copies of deleterious recessive allele
- Not benefit from heterozygote advantage
- Result: Suffer from inbreeding depression

Revision

- Bottleneck <150 = Hatching failure or 25
...
Founder population not as genetically
diverse as source population
...
g
...

- 1930s - Gone from southern Australia & almost
absent in Victoria

- Population founded on bench Island from 2-3
individuals

- Reached carrying capacity
- Used to found Kangaroo Island population (18

identical by decent
...
25

-

Inbreeding Coefficients (f)

- Used to measure degree of inbreeding
- f = Probability of inheriting 2 alleles that are
- If parents are full siblings (Mother/Son & Father/
- If parents are cousins, f = 0
...
g
...
g
...
g
...
g
...

- Captive breeding colony from last 27 birds
- 150-200, some returned to wild
- Recessive lethal alleles has reached a high
frequency (p=0
...
49-0
...
g
...
Culverts

- Unlikely we will have financial or habitat

- Remaining Problem - Persistent inbreeding

- Long-term storage of extracted DNA, seeds,

under highways have reduced problem

-

means most males suffered cryptorchidism
(undescended testes)
- Poorest quality sperm of any cat
- Solution - Introduced 6-8 females from texan
subspecies
...
g
...
5 million live birds
- 640,000 live reptiles
- 1
...
1 million snake skins
- 150,000 pelts from wild furbearers
- 21,000 hunting trophies
- Magnitude of illegal trade difficult to estimate
- Extent of IUU fishing harder to estimate
- Domestic market unregulated “bushmeat”
- ‘Bycatch’ from fisheries; mammals exceed

Revision

- Humans & chimps different by 1% of nucleotides
- Non-coding DNA = 1
...
erectus
-

Poaching
e
...
Traditional Chinese medicine, ivory-trade, outof season deer hunting
Identifying Individuals
- Linking body parts with recovered carcass
- e
...
Bull elk illegally killed in colorado
- e
...
Dead deer found in truck
- Need to ensure probability go genotype in more
than one individual is small

Predictions:
Multiregional

Illegal Trade

-

-

HUMAN EVOLUTION
Origins of Human
- Linnaeus (1707-78) - Term Homo sapiens
- Huxley (1863) discussed similarity between
humans & great ape
- Not popular aT time due to religious reasons
- Hominids & other great apes diverged 5-7
million years ago

Out of Africa

- Single population over

- e
...
caviar from Caspian Sea sturgeon,

ingredients for traditional medicine exotic birds &
fish as pets, hardwood trees from rainforests,
fashion fur, tourist souvenirs
Around 5000 animal & 28,000 plant species
protected by CITES
Species-specific regions of DNA amplified to
identify unrecognisable products
e
...
5%
Sea turtle meat identified & led to conviction of
several restauranteurs
Bushmeat characterisation:
- Hunting for bushmeat can jeopardise
endangered species e
...
Miss Waldron’s red
colobus money
Sharks:
- Dried fins & shark fin soup
Rhinoceroses:
- Powdered material from rhino horn in TCM

to H
...

Gene flow between populations
...

sapiens emerged in Africa then spread out
around globe, replacing other hominids (H
erectus)

-

- If humans expanded

several continents with
gene flow
...
Humans should
show high genetic
diversity
...

All humans expanded
from Africa
...

Locus

Chimp vs
...
Human

Gorilla vs
...
Human

X
Chromosome

3 fold
greater

-

2 fold
greater

3
...
807
0
...
685
0
...
035

0
...
061

2
...
75

1
...
025

0
...


- Eumelanin synthesis associate with black/

- e
...
we can measure genetic distance between

-

- Melanin is the most important pigment affect

0
...

- Lighter skin/hair is derived

0
...
730

X
Chromosome
Sequence

-

- As humans moved out-of-Africa they experience

suggest we owe up to 4% our genome to
Neanderthals
2 ancient lineages of head louse
They diverged 1
...
g
...
e
...
Flattens,
arotenoduds & folate degraded

- Folate deficient can cause neural tube effects

- Positive Effects of UV:
- Synthesis of vitamin D
...
High
vitamin D diet
...

Probably similar in humans
...

- Under strong selection in Africans - Dark
pigment retained
...


- Consumption of milk causes abdominal pain,
diarrhoea etc
...


- Lactase persistence prevalent in Northern
Europe & parts of Central Africa
...

Could it have been under balancing selection
(sickle cell anaemia)
Some evidence that heterozygotes are resistant
to: cholera, typhoid & tuberculosis
∆508 mutation is 10,000-50,000 years old
(phylogenetic analysis)
Geographic distribution suggest European origin

Introduction to Genetics

- Cholera first reported in Europe in 1832
- Typhoid is much older
- Tuberculosis epidemics in Europe due to
-

pastoralism
Conclusion: Reached high frequency in Europe
because heterozygotes are resistant to
infectious disease

QUANTITATIVE GENETICS
Phenotypic Variation
Discontinuous (Categorical)
- e,g
...
g
...
g
...
)



---