Lecture 11(continuation of lecture 10)

Dominance relationships
-Complete dominance
-Dominant traits
-Attached earlobes
-Mid-digital hair
-Phenylthiocarbamide taster
-Inability to straighten little finger
-Hypercholesterolemia
 -Polydactyly
-Inheritance of dominant allele

Recessive pedigree
-Recessive traits
-Albinism
-Sickle cell anemia
-Phenylketonuria

Incomplete dominance

Co-dominance

Epistasis- genes interacting

X-chromosome inactivation(dosage compensation)

Quantitative characters
-Most characters of interest to be
breeders and medics are not controlled by

single (Mendelian) genes but by many genes

and the environment
-Height
-Weight
-Blood pressure
-Diabetes

Obesity
-IQ
-Yield
-Docility
-Speed in a race

Lecture 13
Mapping the Genome

-Linkage- genes together on the same chromosome(not to far apart)- has to be physically on the same
chromosome
-Phenotype: written in roman italics
-Gene name: written in italic script

Testcross data when genes are linked

-AaBb x aabb ——-Expect——> 1 AaBb: 1 Aabb : aaBb : aabb
-But if the A and B allele are stuck together on one chromosome and a and b alleles on the other,
Ab and aB gametes will be rarer than AB and sb gametes

Crossing over(recombination) in meiosis: genes are exchanged between maternal and maternal
chromosome

Calculating the recombination fraction between two genes

Map distance= Number of recombinants/ Total number of progeny x 100

-Recombination factions can be used to measure the distance between genes

-The further apart two genes are the more likely we are to have a recombination of it
-The closer together two genes are the less likely we are to have a recombination of it
-A crossover= ‘Chiasmata’

Recombination fraction
-Unit=centiMorgan=cM
-Thomas Morgan

-You can never get more than 50% recombinants. Therefore maximum recombination fraction is 50

Using recombination fractions to map genes

-We use recombination fractions between pairs of genes to
construct a genetic map that shows how all genes are
positioned on a chromosome
-Genes>50 cM behave as if unlinked, but can still be mapped
on the same chromosome by chromosome walking.
(Sequentially mapping pairs of genes).

Mapping is just a puzzle that allows the known recombination

fractions to coexist

Mapping problem
-Draw a line
-Identify the two genes that are furthest
apart

-Problem is double crossing over

-Because of the double cross over B and Vg
appear as lacking a crossover
-Always use the sum of the shorter recombination fractions

Lecture 15
Genomes and genomics

-A genome is the sum of the genetic information contained within an organism

-Genomes influence every character of an organism: size, disease resistance, allergy, even temperament
and personality
-Genomes give insight into evolution. e.g. Chimpanzees and Humans share 98% of their genomes.
Humans and worms much less.

Comparative cytogenetics
Genome organization-eukaryotes

Genome sizes, gene densities

-Genomes of simple organisms are small and dense-why?
-More complex organisms have more DNA, more genes and more
untranscribed regions
-C-value paradox

Important information can be gained from the different genomes

-Mitochondria
-Phylogenies
-Short term evolutionary studies
-Nuclear
-Phylogenies in deep time
-Understanding of gene function
-Diversity of animals and humans
How a nuclear genome is organized

Gene families

What’s in a (human) chromosome?

-Up to 98% of DNA sequences are untranslated
-Repetitive DNA
-Ribosomal DNA
-Telomeres
-Centromeres

What is the function of the untranslated regions?

-An untranslated region refers to either of two sections, one on
each side of a coding sequence on a strand of mRNA
-UTRs are known to play crucial roles in the post-transcriptional
regulation of gene expression, including modulation of the
transport of mRNAs out of the nucleus and of translation efficient,
sub cellular localization, and stability.

Repetitive DNA
-Genomes are full of repeat sequences
-Minisatellites: about 300 base pair(bp)
sequences are repeated over and over e.g. Alu
sequence
-Microsatellites: 2-3 bro units repeated over and over

Transposable elements(Barbara McClintock)

-Jumping genes
-Code for enzymes that recognize their own DNA sequence, cut them out and allow them to move to
other parts of the chromosome
-Can move other genes along with them
-The genome is loaded with old transposons

Mutation
-3 kinds
-The origin of genetic variance- and of cancers
-Mutation involves changes to the transcribed DNA sequence
-Point (substitution) mutation

-Insertion mutation- this gene will probably be switched off by the insertion

-Deletion

The Polymerase Chain Reaction PCR

-Allows production of any amount of known DNA sequence
-Polymerase from Thermus
aquaticus(extremophile)
-Method for making many copies of
a specific segment of DNA, starting
with a very small amount

Primers- specifically designed oligonucleotides to match DNA around gene of interest

 Some of the things we can do with PCR
-Amplify microsatellites
-Introduce specific mutations to DNA
-Amplify genes from particular animals for sequencing
-Amplify genes across species
-Get DNA for RFLPs
-Amplify ancient/degraded DNA
-Amplify from minute samples
(e.g. a single DNA molecule)

A PCR application 1: Mircosatellites

-Repetitive DNA sequences used as molecular markers in
genetics(e.g. paternity, forensics, population genetics)
-Microsatellite alleles at a given locus vary in length due to
variable number of 1-4 base pair repeats
-Many different microsatellite loci per genome
-Microsatellites alleles are used to genotype individuals
Lecture 16
Population genetics

The structure of populations

 The gene pool
-All alleles, at all loci, in all
individuals
-Alleles, not individuals, are the
units of selection
-Specific alleles(genotypes)
influence survival and reproduction

The Hardy Weinberg Law

-‘Allele frequencies remain the same
from generation to generation to
generation unless acted on by a
force’
-similarity to Newton’s first law
of motion

Allele frequencies define genotype frequencies (but not the other way around)

-We can use allele frequencies to predict genotypic frequencies in a population

-All allele and genotypic frequencies add up to 1

The Hardy Weinberg Law

-Assumptions
-Random mating among individuals
-Large population
-No mutation
-No migration
-No natural selection
-Consider two alleles at tone locus(A and a)
-Frequency of the A allele in the gene pool is p
-Frequency of the a allele in the gene pool is q(
-p+q=1
-So if 75%(0.75) of the alleles at the locus are A, the remaining 25%(0.25) of the alleles must be a
-0.75+0.25=1

NOTE: We are mixing gametes and alleles from the entire population, not just a single Mendelian mating
-Initial allele frees:
-A=p=0.9
-a=q=0.1
Assuming HWE, after one generation of random
mating, calculate predicted genotype frequencies:
AA=p^2=0.9^2=0.81
Aa=2pq=2*0.9*0.1=0.18
aa=q^2=0.1*0.1=0.01

Calculating the frequency of carriers

-Calculating the frequency of carriers in a population
-Frequency of cystic fibrosis in Australia is 1 in
2500 births. CF is a homozygous recessive condition (aa)
aa=q^2 =1/2500
-Therefore, the frequency of the recessive CF allele
is:
-q=√ 1/2500=1/50
-Frequency of normal CF allele is:
-p=1-q
=49/50
-Frequency of heterozygous carriers is:
-2pq
-2*(49/50)*(1/50)
-1/25

Can we eliminate genetic diseases by selection?

-How many deleterious recessive alleles do we all carry?
-Example: 10 diseases each at frequency q=0.01
-P(individual is a carrier for any one=2pq)=0.02
-P(individual is a carrier for any one of the 10)=10*0.02=20%
-Calculations suggest that only 1/3 of the population carriers no lethal equivalents?

Eugenics is a social philosophy which advocates the improvement of human hereditary traits hereditary
traits through various forms of intervention

Allele frequencies remain the same across generations

-Start with frequency A=p in the parental generation
-What is the frequency of A in the next generation?
-In the offspring generation, the total frequency of the A allele is:
Agents of evolutionary change
 Lecture 17
Mechanisms of Evolutionary Change

Mutation
-Raw material evolutionary change
-By definition, a mutation will alter allele frequency in a population(A->a,a->A,A->B)
-Does not have much effect on allele frequencies, especially in large populations
-Differences between populations are not usually due to mutation frequency

Assortative mating
-Non-random mating
-Like mates with like
-May distort H-W equilibrium
 -Produces excess homozygous genotypes
-Does not in itself change allele frequencies

Migration/gene flow
-May introduce new alleles or change existing allele frequencies
-Effect depends on:
-Number of migrants
-Differences in allele frequencies between source and destination

Evolution by migration example

-An initial population of 100 individuals has allele frequencies of p=0.5 and q=0.5 at a locus with 2
alleles (A and a).
Step 1 -What are the initial genotypic frequencies(assuming HWE)?
Step 2 -If the population is invaded by 81 AA, 18 Aa and 1 aa migrants from another population, what
are the new allele frequencies?
Step 3 -Will migration change allele frequencies?

-Step 1
-100 individuals p=0.5 and q=0.5
-f(AA)=p^2=0.25 f(Aa)=2pq=0.5 f(aa)=q^2=0.25
-Aa=0.25*100=25 Aa=0.5*100=50 aa=25
-Step 2
-Step 3
-f(A)=(2*106+68)/(2*200)=0.7

-f(a)=(2*26+68)/(2*200)=0.3
-There was a change in the allele frequencies. The original population 0.5 A

Genetic drift
-Changes in allele frequency caused by chance
-Small populations
-Population crash/ bottlenecks
-Island colonization/ founder effects
-Endangered species and loss of genetic diversity
-Fixation or loss of alleles results in homozygosity

Genetic drift example

Selection
-Non-random survival of alleles in a population
-Artificial, sexual and natural selection
Natural selection
-Different genotypes differ in their fitness, and make disproportionate contributions to the gene pool

Question
-There once was a population of koalas that varied in their expression of a genetically-determined
behavior such that 250 homozygous recessive individuals (aa) always slept on the ground, but the
remaining 750 individuals always slept up in a tree
-One night a flash flood swept through and drowned all the aa koalas sleeping on the ground…

-what were the initial allele and genotype frequencies before selection?
-1000 total koalas
-250 aa ground sleepers
-q=√ (0.25)=0.5
-p=1-0.5-0.5
-but then, selection changed the genotypic (and allele) frequencies:
-“one night a flash flood swept though and drowned all koalas sleeping on the ground”
-so now the surviving population is 750 koalas
-what are the new allele frequencies?
-N=750 koalas
-250 AA and 500 Aa
-f(A)= (2*250+500)/(2*750)=0.67
-f(a)=500/(2*750)=0.33
-what were the genotypic frequencies in the next generation?
-“The surviving koalas randomly mated with each other, giving rise to the next
generation in which the genotypic and phenotypic frequencies of sleeping behavior in the population had
changed”
-f(A)=0.67 f(a)=0.33
-f(AA)=0.67^2=0.45
-f(Aa)=2*0.67*0.33=0.44
-f(aa)=0.33^2=0.11

Types of Natural Selection

Maintenance of polymorphisms: why is there any variation left?
-Heterozygote advantage- heterozygote is better than either homozygote
-Neutral theory: many variants are of no consequence
Heterozygote advantage
-Co-distribution of malaria, sickle cell anemia and thalassemia
-Cystic fibrosis, 1/26 people are carriers
-Debilitating disease (aa)
-Why not selected out?
-Resistance to thyroid fever in heterozygote

Natural theory
-Many changes in DNA sequence do not affect phenotype
-Natural polymorphisms are maintained by a combination of mutation and genetic drift
-Neutral mutations are important as they provide measures of population subdivision (e.g. variation in
microsatellites)
-Provide a molecular clock based on mutation rate

Lecture 18
The evidence for evolution

-Hierarchal organization of life

-Species are most readily classified as a result of divergence and branding from common
ancestors
-Homology(e.g. 1,2, lots of bits, 5 rule)
-Genes and genomes show homology too
-Genes and genomes(e.g. only one genetic code)
-Convergent evolution(e.g. bat wings vs bird wings)
-These are ‘expectations’: using an existing structure and modifying it for a new purpose
-Embryology (embryos of different creatures are similar)
-ontogeny recapitulates phylogeny
-Vestigial organs
-Bodies ain’t perfect
-unintelligent designs
-human eye
-Intermediate forms
-Biogeography
-Fossil record
-Evolution in our lifetimes

-evidence is strong and multi-faceted

-in some ways the evidence is stronger than it is for planetary motion
-certainly stronger than for much of physics
-evolution is falsifiable

Lecture 19
Sex and the single chromosome
Sex and gender in biology
-Biological sex
-Presence/absence of a sex chromosome
-Presence/absence of secondary sexual characteristics (genitalia, plumage etc)
-Size of gametes (sperm/eggs) (over-arching)
Gender(typically human):
-Personal identification as to sexuality
-Social role based on sex: ‘gender roles’

Chromosomal basis of sex determination in mammals, e.g. humans

-Females
-22 pairs of autosomes+XX
-All gametes 22 A+X
-Homogametic
-Males
-22 pairs of autosomes+XY
-Half gametes 22 A+Y
-Half 22A+X
-Heterogametic
-In mammals, males are the heterogametic sex
-males produce two types of sperm: X-bearing and Y-
bearing

-Observing sex ratios do not equal expected

-Expect ratio of males: females to be 1:1
-Actual sex ratios in humans:

Human sex chromosome non-

disjunctions
XO Turner’s syndrome
-1/3500 births
-Female phenotype
-Sterile

Turner’s syndrome
-Late sexual maturity
-Webbing of skin on neck
-Fingernails upturned

XXY Klinefelter’s syndrome

-1/800 births
-Variable male phenotype
-Sterile

XXX Triple X
-1/2000 births
-Female phenotype
-Fertile

XYY-Double Y
-1/550 births
-Normal male phenotype
-Tall
-Claimed to be aggressive and criminal

Molecular basis of sex

-Sex is controlled by the Sex Determining Region Y(SRY) gene

Sex determination in mammals

-Maleness requires:
-Testis determining factor

-SRY locus on Y chromosome

-Receptor for male steroid hormones
 -Androgen receptor on X chromosome

Sex-linked inheritance
-Genes on the part of X and Y that do not pair show sex linkage
-e.g.
color
blindness
-2
alleles
-C normal
-c color blind

-Haemophilia
-When blood can't clot properly, excessive bleeding (external and internal) occurs after any injury
or damage

Costs of sex
-Competing for mates
-Parthenogenetic clone does not break up coadapted gene complexes
-Meiosis and syngamy take 2 x as long as mitosis
-Wasted gametes
-Finding mates at low population densities

Anisogamy
-Sexual asymmetry in gamete numbers and size means eggs are the limiting resource for fertilizations.
The large ratio of male to female sex cells means that numerous sperm must therefore compete for access
to the much rarer ova.

Benefits of sex- DNA repair

-Proof reading when homologous chromosomes pair
-Could have pairing and proof reading without sexual reproduction
Lecture 20
What it means to be a single cell

What is a cell?
-Cell are the fundamental building blocks of life
-most are very small
-All living organisms are made up of
cells and the materials produced by
them
-Cell are small, membrane-bound
compartments in which most
biological reactions occur
-Cells come in very different sizes
-They have the same basic structure
but differ in the details
-Prokaryotes do not have a nucleus
and organelles
-Eukaryotes do have a nucleus and
organelles(mitochondrial(all) and
chloroplasts(plants))

-Animal and plant cells differ in some

key aspect
-Plant cells have a cell wall, which
allows them to grow tall
-But animal cells can change shape

Different kind of microscopes

Biodiversity and tree of life
-Bacteria
-Do not contain a nucleus and rarely harbor membrane-bound organelles
-Archaea
-Membranes composed of glycerol-either lipids. Formerly known as ‘extremophiles’
-Protista
-Unicellular or multicellular that don’t fit into the other kingdoms
(aka left overs)
-Others
-Defined by the way they obtain energy

Most basic functions needed to make a life form

-Heredity
-Compartmentalization
-Metabolism

Basic features of cells

-Bounded by a plasma membrane
-Inside the cell is a semifluid, jelly-like
substance called cytosol
-DNA is stored in a nucleoid (prokaryote) or
nucleus (eukaryote)
-The cell’s interior is called the cytoplasm
-Proteins are produced in the ribosomes
-The cytoskeleton supports and maintains the cell’s shape

Prokaryotic cell

Plant cell
Animal cells
-Living organisms are made up of cells and cell products
-Prokaryotic cells have a simple structure and lack internal compartments
-Eukaryotic cells contain intracellular, membrane-bound compartments, which separate different
molecules and metabolic reactions
-The structure, organization and dynamics of sub cellular components can be studied using a variety of
light and electron microscopy techniques

Animal versus plant

-Plant cells have a cell wall and a central vacuole
-Animal cells do not have chloroplasts

Main functions of cell wall

-Rigidity and strength: allows plants to grow tall and hold out their leaves to capture light
-Physical barrier: protection
-Maintains the shape and structure of the cell wall

Main functions of central vacuole

-Maintain water pressure: turgor pressure(the central vacuole can occupy between 30-80% of the total
volume of the cell)
-Allows the cell to expand

What is possible without a rigid cell wall

-Phagocytosis

-Linking plant cells

-Plasmodesmata
-Microscopic channels which traverse
the cell wall of plant cells
-Enables transport and communication
between cells
-Basically turns a plant into one living
continuum
-Linking animal cells
-Tight junctions
-Form a seal around the
cell
-Extracellular matrix
-Some similarities with plant cell wall
-Desmosomes
-Fasten the cells together into strong sheets

-Gap junction
-Similar function to plasmodesmata in
plant cells

Why so many plants are tall

-Terrestrial communities are often light limited
-Selection pressure on plants to become taller
-Animals: just move around to eat
-Although sharing some similarities with the extracellular matrix of animal cells, plant cells, constitute an
important difference between animal and plant cells
-Plant cell wall inhibit cell movement and have a major influence on many aspects of plant growth and
development