Genes during development

Development Involves Distinct but Overlapping Processes

Development—the process by which a multicellular organism
undergoes a series of changes, taking on forms that
characterize its life cycle.
After the egg is fertilized, it is called a zygote.
In its earliest stages, a plant or animal is called an embryo.
The embryo can be protected in a seed, an egg shell, or a uterus.
Four processes of development:
• Determination sets the fate of the cell
• Differentiation is the process by which different types of cells
arise
• Morphogenesis is the organization and spatial distribution of
differentiated cells
• Growth is an increase in body size by cell division and cell
expansion
Development in Multicellular Organisms

Multicellular Organisms made of differentiated

cells undergo development after fertilization.
Fertilization may occur in a variety of ways.
For many Fungi, once the hyphae of two strains
come in contact, their cells fuse, creating the
zygote (2n). Generally this develops into the
diploid fruiting body that releases spores. Few
cells differentiate to produce the spore-
producing cells. (2nn)
When spores germinate, hyphae (collectively
known as mycelium) radiate out in a circular
pattern of undifferentiated haploid cells.
Development in Multicellular Organisms

More complex organisms such as

plants and animals have a much
more complex development.
Development Involves Distinct but Overlapping Processes

As a zygote develops, the cell fate of each undifferentiated cell drives it to become part of a
particular type of tissue.
Experiments in which specific cells of an early embryo are grafted to new positions on another
embryo show that cell fate is determined during development.
Determination is influenced by changes in gene expression as well as the external environment.
Determination is a commitment; the final realization of that commitment is differentiation.
Differentiation is the actual changes in biochemistry, structure, and function that result in cells of
different types.
Figure 14.1 Development (Part 1)
Fertilization occurs-
A wave of Ca2+ release during the cortical reaction- part of the process that prevents
polyspermy, the zygote is formed.
Figure 47.8x Cleavage in a frog embryo- the resulting mass of cells (bottom right) is called the Morula.
Figure 47.8d Cross section of a frog blastula – essentially the morula with a cavity known as the blastocoel
Figure 47.20 Fate maps for two chordates
Table 47.1 Derivatives of the Three Embryonic Germ Layers in Vertebrates
Development Involves Distinct but Overlapping Processes
Development Involves Distinct but Overlapping Processes
Determination is followed by differentiation—under
certain conditions a cell can become undetermined
again.
It may become totipotent—able to become any type of
cell, including extraembryonic cells (placental). Most
plant cells are totipotent. Differentiated animal cells
can be manipulated to be totipotent (used in cloning).
Pluripotent - cells in the blastocyst embryonic stage
retain the ability to form all of the cells in the body.
Multipotent—they produce cells that differentiate into a
few cell types. Multipotent stem cells differentiate “on
demand.”
Stem cells in the bone marrow differentiate in response
to certain signals, which can be from adjacent cells or
from the circulation.
Figure 14.6 Two Ways to Obtain Pluripotent Stem Cells

Major controls of gene expression in

differentiation are transcriptional
controls.
While all cells in an organism have the
same DNA, it can be demonstrated
with nucleic acid hybridization that
differentiated cells have different
mRNAs.
Two ways to make a cell transcribe
different genes:
• Asymmetrical factors that are
unequally distributed in the cytoplasm
may end up in different amounts in
progeny cells
• Differential exposure of cells to an
external inducer
Changes in Gene Expression Underlie Cell Differentiation in
Development
Polarity—having a “top” and a
“bottom” may develop in the embryo.
The animal pole is the top, the vegetal
pole is the bottom.
Polarity can lead to determination of
cell fates early in development.
Polarity was demonstrated using sea
urchin embryos.
If an eight-cell embryo is cut vertically,
it develops into two normal but small
embryos.
If the eight-cell embryo is cut
horizontally, the bottom develops into
a small embryo, the top does not
develop.
Changes in Gene Expression Underlie Cell Differentiation in
Development
In sea urchin eggs, a protein
binds to the growing end
(+) of a microfilament and
to an mRNA encoding a
cytoplasmic determinant
(RNA or protein).
As the microfilament grows
toward one end of the cell,
it pulls the mRNA along.
The unequal distribution of
mRNA results in unequal
distribution of the protein it
encodes.
This results in cells with
different fates.
Concept 14.2 Changes in Gene Expression Underlie Cell
Differentiation in Development
Induction refers to the
signaling events in a
developing embryo.
Cells influence one another’s
developmental fate via
chemical signals and signal
transduction mechanisms.
Exposure to different amounts
of inductive signals can lead
to differences in gene
expression.
Concept 14.2 Changes in Gene Expression Underlie Cell
Differentiation in Development
Induction involves the
activation or inactivation of
specific genes through
signal transduction
cascades in the
responding cells.
Example from nematode
development:
Much of development is
controlled by the
molecular switches that
allow a cell to proceed
down one of two
alternative tracks.
Spatial Differences in Gene Expression Lead to Morphogenesis

Pattern formation—the process that results

in the spatial organization of tissues—
linked with morphogenesis, creation of
body form
Spatial differences in gene expression
depend on:
• Cells in body must “know” where they are
in relation to the body.
• Cells must activate appropriate pattern of
gene expression.
 Development and Genes Part II
Pattern Formation and Morphogenesis
Using Drosophila as a Model Organism for
Devlopment

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Using Drosophila as a Model Organism for
Devlopment

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Using Drosophila as a Model Organism for
Devlopment

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Example: Drosophila Pattern Formation for the
Posterior-Anterior Axes
Christane Nüsslein-Volhard and Eric
Wieschaus undertook a project to discover the
genetic mechanisms of how a fertilized
Drosophila egg became a segmented embryo.
Drosophila larvae begin segmentation shortly
after fertilization, as the cells organize into
fourteen distinct body segments.
To investigate this process, Nüsslein-Volhard and
Wieschaus exposed fly embryos to mutagens, and
systematically characterized their phenotypic mutations.
They screened mutated embryos that exhibited abnormal
development of the body axis or segmentation to identify
which genes had gone awry.

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 Example: After Segmentation,
Segments are Specialized
In normal flies, structures like legs, wings, and
antennae develop on particular segments, and
this process requires the action of homeotic
genes. Ed Lewis (1940’s), who discovered
homeotic mutants - mutant flies in which
structures characteristic of one segment of the
embryo are found at some other segment.
In normal flies, structures like legs, wings, and
antennae develop on particular segments, and
this process requires the action of homeotic
genes.
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 Example: Drosophila development of body
structures
Edward Lewis (1918-2004) discovered that the
genes that provided the code for the fly's body
were segmented and ordered, even in the
embryo stage. These genes dictated the
development of each segment of the body. By
causing mutations in certain genes, he found
that he could cause flies to grow extra body
parts or other abnormal features. Homeotic
genes are genes which regulate the
development of anatomical structures in
various organisms such as insects,
mammals, and plants. 26
The homeotic genes encode
transcription factors that control the
expression of genes responsible for
particular anatomical structures, such as
wings, legs, and antennae. The homeotic
genes has a subsection which includes a
180 nucleotide sequence called the
homeobox (also called hox genes),
which is translated into a 60 amino acid
domain, called the homeodomain. The
homeodomain is involved in DNA
binding.
27
A homeoprotein or HOX protein contains a
homoedomain (in red). It is the
homeodomain (60 amino acids long) that
interacts with the DNA as a transcription
factor for a particular gene needed in
development.

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Hox genes are switched on in different segments. Patterns
of Hox gene activity give each segment an identity,
telling it where it is in the body and what structures it
should grow. For instance, genes that are active in the
head direct the growth of mouth parts and antennae, while
genes that are active in the thorax direct the growth of
legs and wings.
Drosophila, like all insects, has eight Hox genes. These
are clustered into two complexes, both of which are
located on chromosome 3.

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Interestingly, Hox genes are arranged in clusters.
Typically, their order on the chromosome is the
same as the order in which they appear along the
body. In other words, the genes on the left
control patterning in the head, and the genes on
the right control patterning in the tail.

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Changes to Hox gene
expression change a
segment’s identity. For
example the first segment
of the thorax normally
grows legs, the second
grows legs and wings, and
the third grows legs and
halteres. When the Hox
gene activity in the third
segment is made the same
as that in the second, both
segments grow legs and
wings.
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On the right is
the normal
development,
and on the left
is the mutant.

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 Evolution and
Importance of Hox
Genes

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Example of
Hox Gene

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Example of Hox Gene Developmental Mutations

Evolution of the
Hox genes

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Pattern Formation and
Morphogenesis

These are the hox genes that

control certain vertebrae and
their development.
Once the body pattern is
established, and then
morphogenesis can occur,
which is the formation of
various organs and systems

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37
 Morphogenesis Can Involve Cell Death Occurs

Apoptosis occurs in the development of the digits of a

hand or paw. Shown is the development of a mouse
paw.
The genes that regulate apoptosis are similar in both
vertebrates and invertebrates such as nematodes.
Fungi including yeast also have genes that regulate
apoptosis indicating these are ancient genes. 38
During Development Cell Death Occurs

Apoptosis- Is a programed
cell death. Occurs in
•Infected cells
•Development
•Cells that are aged and no
longer functional
The cell below is a normal
leukocyte and the cell above
is a cell undergoing apoptosis

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 Heterotrophy
Shown is the development of the hind limb of
chicken versus a duck. The duck retains the
webbing between the digits.

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Heterochrony

Heterochrony is
the regulation of
developmental
stages by
changing the
duration of the
developmental
process
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The one of the differences between the plain
zebra and Grevy zebra is that the Grevy zebra
has more narrow stripes. It is thought that the
genes responsible for the stripes are delayed in
the plain zebra, resulting in wider stripes.
Timing in development is very important.

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Neighboring Tissues
Can Effect
Morphogenesis

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Genes on the Y chromosome can
influence morphogenesis

There is primordial tissue that is

destined to become gonads. In
mammals the sex-determining
region Y (SRY) gene on the Y
chromosome will cause the
development of testis. Without
the presence of the SRY protein
the tissue will develop into
ovaries no matter the
chromosomal condition.
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Genes on the Y chromosome can influence
morphogenesis

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Effect of Testosterone on
Development

46
 Cloning using adult
differentiated cells
While it was thought
that differentiated adult
cells could not be used
to make a clone because
genes had been
permanently inactivated.
In 1997 researchers at
the Roslin Institute were
able to clone a lamb
from an adult
differentiated cell.
47
Developmental Genes Contribute to Species Evolution but Also
Pose Constraints

Many developmental genes exist in similar

form across a wide range of species.
Highly conserved developmental genes
make it likely that similar traits will evolve
repeatedly: Parallel phenotypic
evolution.
 3’-WUT ATI ONS-5’
5’-MUTATIONS-3’

21^3
XO
XXY
@LAYSOGUI
 MUTATION

• Process that produces alteration in DNA

or chromosome structure
• It is also a failure to store the genetic
information faithfully
• It includes both chromosomal changes
collectively known as chromosome
aberration or changes within a single
genes called GENE MUTATIONS
CLASSIFICATION OF MUTATIONS
• 1. Spontaneous Mutations
• Those that just happen in nature; no specific agents associated with
its occurrence and generally assumed to be random changes in the
nucleotide sequences of genes; linked to normal chemical processes
in the organism that alter the structure of the nitrogenous bases
especially during DNA replication.

• 2. Induced Mutations
• Those that result from the influence of any artificial factor i.e.
radiation from cosmic and mineral sources, UV exposure from the sun
and other chemical agents.
 Molecular Basis of Mutation
• Gene is a linear sequence of three nucleotide pairs representing stored chemical information
• Genetic code is a triplet and each sequence of 3 nucleotides specifies a single amino acid
• Any change that disrupts these sequences or the coded information provides sufficient basis for
mutation

1. Base Substitutions or Point mutations: TRANSITION (A-G, T-C) vs TRANSVERSION (A-T, C-G)
2. Frameshift mutations
Example: THE CAT SAW THE DOG
Change of one letter Loss of one letter Gain of one letter
SUBSTITUTION DELETION INSERTION
THE BAT SAW THE DOG THE ATS AWT HED OG THE CMA TSA EDO G
THE CAT SAW THE HOG loss of C insertion of M
THE CAT SAT THE DOG

POINT MUTATION FRAMESHIFT MUTATION FRAMESHIFT MUTATION

NONSENSE MUTATIONS vs MISSENSE
MUTATIONS
Is any genetic mutation that leads to the RNA Is a genetic mutation that changes amino
sequence becoming a stop codon instead.
acid to another.

DNA RNA PROTEIN DNA RNA PROTEIN

ACA ACA
UGU UGU
Cysteine Cysteine

ACT UGA ACC UGG

Stop Tryptophan

Nonsense mutations probably affect the resulting protein a lot more than missense mutations
do. Since that new STOP codon that we’re creating could dropped off a huge section of a
protein instead of just changing one amino acid to another.
CATEGORIES MISSENSE MUTATIONS
• SILENT MUTATIONS-do not actually affect the proteins at all since many different
RNA codons could code for the same amino acid
i.e. CCA, CCG, CCT, CCCGlycine

• CONSERVATIVE MUTATIONS- it is when the new amino acid is on the same type as
the original
i.e. Glutamic acid Aspartic acid

• NON-CONSERVATIVE MUTATION- when the mutation resulted to the different type

of amino acid from the original
i.e. Serine Phenylalanine
small polar AA large nonpolar amino acid
SICKLE CELL: Point mutation, non-
conservative

Glu Val
SUMMARY

• 1. MUTATIONS ORIGINATE AT THE DNA LEVEL, BUT

SHOW THEIR EFFECTS AT THE PROTEIN LEVEL.

• 2. MUTATIONS CAN BE CLASSIFIED BY EITHER THEIR

EFFECTS ON DNA OR ON PROTEIN.
DNAPoint and Frameshit
PROTEINMissense and Nonsense
SUMMARY
❑ GENE MUTATIONS (POINT MUTATIONS)
1. Base substitutions
2. Base insertions
3. Base Deletions
❑ CHROMOSOME MUTATIONS
❖ Changes in chromosome structure
1. Chromosomal deletion: when a section of a chromosome is missing
2. Chromosomal duplication: when a section of a chromosome is repeated
3.Chromosomal Inversion: when a section of a chromosome is inverted
4. Chromosomal Translocation: when a section of a chromosome breaks off and reattaches
to another non-homologous chromosome
❖ Changes in chromosome number
1. Non-disjunction: Trisomy 21, XXY, XO, XXX, XYY
 KARYOTYPING
• One of the techniques that allows us to diagnose several thousand possible genetic diseases in
humans.
• Refers to the use of microscope to examine the size, shape and number of chromosomes in a
sample of body cells.
• KARYOTYPE is the number and visual appearance of the chromosomes in the nucleus of a cell