Topic 3.1 to 3.

8
Year: IAS
Subject: Biology
Unit: 3
Learning Objective

 Content:
 Skill:
 Criteria for Success:
 What are we trying to Do, Say, Make or Write?
3.16 Be able to calculate mitotic indices

Mitotic Index

 A measure of the proliferation status of a cell population

 The proportion of dividing cells (Cells in mitosis / total number of cells)
 Will increase during processes that promote mitosis, such as normal
growth or cellular repair
 Prognostic tool for predicting the response of cancer cells to
chemotherapy (the higher the mitotic index, the bigger the response)
Calculating the Mitotic Index

 You first need to be able to discern cells undergoing mitosis

 Then count them

 Then divide that number by the total number of visible cells
Calculating the Mitotic Index: Exercise

Only count the cells where the whole nucleus is visible

3.17 (i) understand what is meant by the terms stem cell, pluripotent
and totipotent, morula and blastocyst

 All cells arise from the stem cells.

 Stem cells are specialised cells that can give rise to other cells.
 Cell differentiation is a process by which the stem cells divide by mitosis and
give rise to other, specific cells.
 This ability of stem cells to differentiate into other cell type is called potency:
 Totipotency: The ability of stem cells to differentiate into all kinds of cells
including the embryonic cells is called totipotency.
 Pluripotency: The ability of stem cells to differentiate into all kinds of cells
but not embryonic cell is called pluripotency.
 Blastocyst: A mammalian blastula in which some differentiation of cells has
occurred.
 Blastula: An animal embryo at the early stage of development when it is a
hollow ball of cells.
 Morula: A solid ball of cells resulting from division of a fertilized ovum.
3.17 (ii) be able to discuss the ways in which society uses scientific
knowledge to make decisions about the use of stem cells in medical
therapies

 Stem cells can be harvested from embryos, cord blood cells or adult cells (which
are reprogrammed in totipotent cells).
 The cells can then be used to replace cells / repair tissues.
 Example: Stargardt’s macular dystrophy

FYI The problem • Affects around one in 10,000 children

• Recessive genetic (inherited) condition
• The mutation causes an active transport protein on photoreceptor cells to
malfunction
• The photoreceptor cells degenerate
• the production of a dysfunctional protein that cannot perform energy transport
• that causes progressive, and eventually total, loss of central vision

The • Embryonic stem cells are treated to divide and differentiate to become retinal
treatment cells
• The retinal cells are injected into the retina
• The retinal cells attach to the retina and become functional
• Central vision improves as a result of more functional retinal cells
The future • This treatment is still in at the stage of limited clinical trials, but will likely be in
usage in the future
Example of scientific knowledge to make decisions
about the use of stem cells (FYI)

Comparison of stem cell sources

Embryo Cord blood Adult
Differentiation Can differentiate Limited capacity Limited capacity
into any cell type to differentiate to differentiate
(without (dependent on the
inducement only source tissue)
naturally divide
into blood cells)
Genetic damage Less chance of genetic damage than Due to
adult cells accumulation of
mutations through
the life of the
adult genetic
damage can occur
Compatibility Stem cells are not Fully compatible with the patient as
genetically the stem cells are genetically identical
identical to the
patient
3.18 Understand how cells become specialised through differential gene
expression, producing active mRNA, leading to the synthesis of proteins
which, in turn, control cell processes or determine cell structure in
animals and plants

 Specialized tissues can develop by cell differentiation in multicellular

organisms.
 All (diploid) cells of an individual organisms share an identical genome -
each cell contains the same chromosomes and genes (the entire set of
genetic instructions for that organism)
 BUT: not all genes are expressed (activated) in all cells (except for
embryonic stem cells: they are totipotent and their entire genome is
active)
 Cell differentiation involves the expression of some genes and not others
in a cell’s genome. Specialized cells (unipotent) only have a part of their
genes that is active.
 Example: a skin cell does not need to be able to produce haemoglobin
(the protein in red blood cells that carries oxygen).
Specialized tissues can develop by cell differentiation
in multicellular organisms

 In humans 220 distinct highly specialised cell

types have been recognised
 All specialised cells and the organs
constructed from them have developed as a
result of differentiation
 Active genes are usually packaged in an
expanded and accessible form
(euchromatin), while inactive genes are
mainly packaged in a condensed form
(heterochromatin)
 The fewer active genes a cell possesses the
more specialised it will become
 As a result of gene expression, cell
differentiation begins: the cell’s
metabolism and shape changes to carry out
a specialised function.
3.18 Understand how cells become specialised through differential gene
expression, producing active mRNA, leading to the synthesis of proteins
which, in turn, control cell processes or determine cell structure in
animals and plants

 Transcription and translation, inheritance: see topic 2!

 FYI: How gene expression is regulated

The repressor protein is bound

RNA Polymerase
to the operator preventing RNA
Polymerase from transcription
of the genes

DNA Strand

Operator is a region of DNA that Gene

can regulate transcription,
typically inhibiting
transcription, such as this
silencer sequence.

The promoter is a DNA

sequence is located near a
gene. It acts as the binding
site for RNA polymerase.
 3.19 Understand how one gene can give rise to more than one protein
through post-transcriptional changes to messenger RNA (mRNA)

Eukaryotic genes (unlike prokaryote) contain base sequences that are not translated
into polypeptides

Exons are coding sections of the gene.

Introns are removed then broken down

back into nucleotides ready for use.
They are the non-coding sections of
genes.

Mature mRNA contains only exons

leaves the nucleus to be translated into
polypeptides.

The Spliceosome forms and causes

the introns to form loops which allows
the exons to be joined
The splicing process can happen in different ways (alternative splicing). Particular
exons (of a gene) may be included within or excluded from mature mRNA before it is
translated into a protein.

One gene can be spliced into different proteins. Example: immunoglobulins

(antibodies): a lot of different antibodies have to be created to recognize different
pathogens.

https://commons.wikimedia.org/wiki/File:DNA_alternative_splicing.gif
3.20 (i) understand how phenotype is the result of an interaction between genotype and the environment

 Genotype, phenotype, allele: see 2.15

 The phenotype isn’t only determined by the genotype
 The environment to which someone is exposed, his personal experiences, and
random events also influence the phenotype
 Example: monozygotic twins, who are genetically identical, always have some
differences in appearance and the way they act
 Some genes are activated or inactivated depending on the environment
 Example: Human hair and skin colour (molecules called « morphogens » are
activated by sunlight and modify the expression of the gene that leads to the
production of melanin)
 Some environmental factors can damage / modify the DNA (viruses, radiation,
smoke, the food we eat, etc.).
(ii) know how epigenetic modification, including DNA methylation and histone
modification, can alter the activation of certain genes
(iii) understand how epigenetic modifications can be passed on following cell
division

The epigenome refers to the non-DNA structures that

affect the gene expression.

Eukaryotic DNA supercoiling prevents the genes from

being accessible (by the RNA polymerase) and,
therefore, the corresponding proteins can’t be
produced.
The genes are referred to as “inactivated” or
“unexpressed”).
The supercoiling is organised by nucleosomes.

• Nucleosomes both protect DNA and allow it to be packaged,

this in turn allows DNA to be supercoiled.
• Nucleosomes are formed by wrapping DNA around histone
proteins

n.b. Prokaryotic DNA is not organised by histones and is therefore

sometimes referred as being ‘naked’.
Structure of a simplified nucleosome (FYI)

octamer (contains two copies of four different types of

histone protein)

The H1 histone binds DNA in a way that facilitates

further coiling.

http://commons.wikimedia.org/wiki/File:Nucleosome_organization.png
http://en.wikipedia.org/wiki/File:DNA_to_Chromatin_Formation.jpg
Histones, methyl groups and acetyl groups are part of the epigenome

NB: Methylation is the addition of methyl groups to DNA, Acetylation is the

addition of Acetyl groups to histones

Both can affect transcription depending on whether or not they help

histones bind more or less to the DNA.

Changes in the environment can directly or indirectly affect processes such as

Acetylation & Methylation and, therefore, gene expression.

Edited from: http://www.nature.com/neuro/journal/v13/n4/images/nn0410-405-F1.jpg

Reprogramming erases most of the epigenetic tags to return the cells to a genetic "blank slate”.

Mitosis does not modify the epigenom and that is why a specialized cell can produce two identical
specialized cells (« epigenetic memory »).
3.21 Understand how some phenotypes are affected by multiple alleles
for the same gene, or by polygenic inheritance, as well as the
environment, and how polygenic inheritance can give rise to
phenotypes that show continuous variation

Polygenic Inheritance
Polygenic: multiple genes affecting ONE phenotypic trait (single characteristic)

Polygenic inheritance gives rise to continuous variation in the phenotype.

Examples:
• Human skin colour
• Wheat kernel colour
• Susceptibility to heart disease, certain types of cancer,
mental illnesses.
• The Autism Spectrum.
(It is suspected that gene interactions and environmental factors play a
large role in the degree of autism).
Polygenic Inheritance of Skin Colour

• Globally we observe continuous variation in skin colours.

• Skin colour is the result of pigments, such as melanin, being produced - the
darker the skin, the greater the protection against the harmful effects of the
Sun.
• Skin colour is thought to be controlled by up to four separate genes, each
with their own alleles.
• This is too large for us to deal with simply, so we'll look at two genes with
two alleles each.
Polygenic Inheritance of Skin Colour
Example: 2 genes (A and B), 2 alleles each
Assume: genes are not linked (separate chromosomes)
Key to alleles:
In polygenics, alleles can be: A = add melanin
• Contributing (they add to the phenotype) a = don’t add melanin
• Non-contributing (they do not add to the phenotype) B = add melanin
b = don’t add melanin

o o o
r r r Reminder:
Alleles of unlinked
chromosomes orient
randomly.
There is also random
fertilisation of gametes.
gametes
So many combinations!
Polygenic Inheritance of Skin Colour
IL: construct a Punnet Grid to show all possibles crosses with the 4 dihybrid
gametes (on the previous slide) to show how the following genotypes (9
different!) were found:

There are 9 possible genotypes (aabb, Aabb, aaBb, Aabb, aaBB, AaBb, AaBB, AABb and AABB)
There are either 0, 1, 2, or 4 alleles that add melanin, leading to 5 degrees of skin colour
If we were to consider 4 genes, the degrees would be much greater: CONTINUOUS VARIATION

NB: This population follows a normal distribution.

Environmental factors affecting the
genotype
 Most traits, including polygenetic traits such as height, maybe influenced by the
environment of the organism. There are numerous ways in which this can happen.

Human Trait Influencing Environment factors

Height • Dietary factors (e.g. protein content)

• Certain childhood diseases

• Exposure to sun
Skin colour • Burns
• Scaring
Polygenic Inheritance of Skin Colour
Is it possible for a baby to be lighter or darker than both parents? Key to alleles:
A = add melanin
a = don’t add melanin B =
add melanin
F0 Phenotype: b = don’t add melanin

Genotype: AaBb AABb

Punnet Grid: gametes AB AB Ab Ab
darker
AB AABB AABb AABb
AABB
Ab AABb AABb AAbb AAbb
aB AaBB AaBB AaBb AaBb
lighter
ab AaBb AaBb Aabb Aabb

F1 Genotypes:
Phenotypes:
3.15 CORE PRACTICAL 6
Prepare and stain a root tip squash to observe the stages of mitosis.

https://www.youtube.com/watch?v=5-ur7bWqlDQ
IL: answer this past exam question
IL: inheritance, review exercise (see
topic 2)
 Consider 2 genes (unlinked) in 2 parents that affect their skin colour. One is
heterozygous for both genes (one allele contributing to skin melanin
production and one that doesn’t) and one is homozygous dominant (all alleles
contribute to melanin production) for both genes.
 What are the possible genotypes and their likelihood for their children?
Independent Learning

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Plenary
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