D2.

2 Gene Expression HL Notes

Gene expression as the mechanism by which information in genes has effects on the
phenotype
• Gene expression is the process by which genetic information is used to produce
mRNA and proteins.
• The proteins produced by an organism determines its phenotypes.
• A phenotype is an observable trait of an organism resulting from genotype and
environment factors.
• Cells produced by fertilisation and during early embryonic development are
unspecialised because they express far fewer genes than differentiated cells .
• As cells mature and differentiate, variations in the level of expression of different
genes between cells enables them to exhibit diverse structures and functions
required for their specialised roles.
• Therefore, although the genotype of a cell does not change, its functions will.
Common stages in gene expression
• Transcription: the DNA sequence of a gene is used as a template to synthesise a
complementary RNA molecule called messenger RNA (mRNA)
• Translation: the mRNA molecule is read by ribosomes to produce a protein product
• The protein produced through transcription and translation carries out specific
functions either inside or outside of the cell, such as enzymatic activity, signalling and
transport.

Regulation of transcription by proteins that bind to specific base sequences in DNA

• On the DNA, just before a gene, is a region of code known as the promoter
• At the promoter, proteins known as transcription factors can bind.
• It is the binding of the correct transcription factors in the correct orientation that
allows the RNA polymerase to also bind and then begin to transcribe the DNA into
RNA.
• If those transcription factors are missing or something has blocked their ability to bind
to the promoter, transcription will not take place and that gene cannot be expressed.
• Promoter regions occur on DNA strands just before the start of a gene’s sequence of
bases.

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 • The transcription of the template strand of the gene begin only when this
transcription complex of proteins has been assembled.
• Specific transcription factors bind at the enhancer to increase (or decrease) the rate
of transcription.
• Enhancers are located upstream of the promoter and gene sequence.
• Binding of activator proteins to the enhancer site forms a new complex that can
contact the promoter-transcription factor complex.
• This increases the rate of transcription.
Control of the degradation of mRNA as a means of regulating translation
• mRNA molecules are synthesized during the process of transcription.
• The mRNA is examined, modified and transported to ribosomes, before eventually
being translated into proteins.
• mRNA is eventually broken down (degraded) by nucleases.
• The 3' poly-A tail must be degraded before the mRNA is broken down.
• When the mRNA is no longer being used for translation, poly-A tail shortening is one
of the key steps initiating degradation of the mRNA.
• Degradation of mRNA ensures that proteins are synthesized only when they are
needed, and that mRNA is removed once its job is done.

Epigenesis as the development of patterns of differentiation in the cells of a multicellular

organism
• Epigenesis refers to the development of an organism by differentiation from an
undifferentiated zygote.
• It is the development of patterns of differentiation in the cells of a multicellular
organism.
• Epigenesis is determined by the genome of an organism and gene expression.
• Environmental factors can change the activity of genes and these changes can be
passed on to the offspring, affecting their development.
Epigenetics
• Epigenetics is the study of heritable changes in gene activity that are not caused by
changes in the DNA base sequences. Mechanisms that produce such changes are
DNA methylation and histone modifications.
• Phenotype refers to the characteristics or appearance of an organism which is
determined by the genotype (Genetic code of an organism).

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 • Genotype is the combination of alleles inherited by an organism.
• DNA base sequences are not altered by epigenetic changes, so the phenotype, but
not the genotype, is altered.

Differences between the genome, transcriptome and proteome of individual cells

• The Proteome of an organism refers to all the proteins expressed within a cell, tissue
or organism at a certain time.
• The proteome varies with the function, location or environmental conditions of the
cell through the process of cell differentiation. It varies and is dynamic due to gene
expression.
• Genome is whole of the genetic information of an organism, is unique to each
individual.
• Genome is the same in all the cells of an organism because all cells in the
multicellular organism are ultimately derived from one original cell by cell division.
• The genome instructs the expression of proteins. Different proteins are expressed in
each specific tissue cell type related to their function.
• For e.g specific organs in the gut synthesize digestive enzymes, collagen is produced
in bone and other skeletal structures.
• All genes are not expressed in a cell, the process of gene expression requires energy,
so it is more efficient to switch on only the genes that are needed.
• Specific genes are therefore expressed (turned on or off) in different cells according
to a required function.
• The transcriptome is the range of mRNA transcripts produced in a specific cell or
tissue type at a particular time which depends on the differential expression of genes
within a cell.
• The transcriptome will determine which proteins are synthesized with in a cell, which
in turn depends on which parts of the genome are activated via gene expression.
Nucleosomes -review
• Eukaryotic DNA is packaged and organised around histone proteins to form compact
structures called nucleosomes.

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 • Nucleosomes play a fundamental role in regulating chromatin structure and
accessibility to transcriptional machinery.
• Histone proteins consist of a core domain and a tail region.
• The core domain forms the central part of the nucleosome, around which DNA is
wrapped, and the tails (N-terminal regions of the proteins) protrude outwards.
• Histone proteins have a net positive charge, with their tail regions containing a high
density of positively charged amino acids.
• The resulting attraction between the negatively charged DNA and the positively
charged histone tails facilitates the formation of nucleosomes and compact
chromatin formation.
Heterochromatin and Euchromatin
• When DNA is supercoiled (wrapped tightly) around histone proteins, it forms a
condensed structure called heterochromatin.
• In this state, the DNA is less accessible to RNA polymerase and other transcription
machinery, resulting in reduced transcription.
• When DNA is loosely packed around histone proteins, it is called euchromatin.
• Euchromatin is more accessible to RNA polymerase and other transcription
machinery, resulting in increased transcription and enhanced gene expression.
Methylation of the promoter as an example of epigenetic tag
• Methylation is the reversible addition of a methyl group (- CH3) sometimes to histone
tails but usually to the DNA molecule at the promoter region.
• Methylation of cytosine in the DNA of a promoter represses transcription because it
prevents transcription factors from binding.
• These are known as epigenetic tags (chemical tags such as methyl or acetyl groups
that are added directly to DNA or on to histone proteins to regulate gene expression,
blocking or allowing access to a gene's 'on' switch).

Methylation of histone in nucleosomes as an example of epigenetic tag

• Methylation of amino acids in histone tails either enables or disables the recruitment
of regulatory proteins to the chromatin, causing transcription to be repressed or
activated.
• Once the gene is methylated, it remains in this condition. The methyl groups persist
in situ from cell division to cell division.
• Removal of methyl groups may turn genes back on again.

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Epigenetic inheritance through heritable changes to gene expression
• Epigenetic inheritance refers to the inheritance of non-genetic information that can
influence gene expression and phenotypic traits.
• For epigenetic inheritance to occur during sexual reproduction, epigenetic changes
such as DNA methylation or histone modification must occur in germline cells, and be
maintained during meiosis (spermatogenesis and oogenesis) and passed on to the
offspring.
Examples of environmental effects on gene expression in cells and organisms
• Exposure to air pollution, such as nitrous oxides, and particulate matter such as soot
has been shown to affect the DNA methylation patterns of genes involved in
inflammation, oxidative stress and immune response pathways.
• This can result in a disruption of normal cellular processes, increased inflammation,
increased risk of oxidative damage and a more susceptible immune system.
• Interstitial lung diseases (ILDs) is an overall term for diseases that cause inflammation
of tissues within the lung, including the bronchioles, alveoli and the capillaries
surrounding the alveoli, leading to scarring and thickening of tissue.
• ln the alveoli, thickening of tissue can lead to decreased rates of oxygen diffusion into
the blood.
• Inflammation of the bronchioles causes asthma.
• Hypersensitivity pneumonitis (HP), one of the most common forms of lLD, is
triggered by the inhalation of organic and inorganic substances from air pollution.
These pollutants influence HP development through epigenetic modifications.
• Treatments, such as exercise and B vitamins, have been suggested as solutions to
reduce the impact of air pollution on methylation patterns and health.
Consequences of removal of most but not all epigenetic tags from the ovum and sperm
• Many organisms retain and pass on epigenetic marks from environmental exposure
via gametes to the next generation.
• Shortly after fertilisation, the majority of epigenetic tags are removed from the
parental DNA.
• This resets the epigenetic environment of the genome by eliminating genetic
modifications that have occurred during the lifespan of the parents.
• It also allows for the development of new epigenetic modifications so that cells can
differentiate into various cell types

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 • For approx. 1% of genes, however, epigenetic tags pass unchanged from parent to
offspring, through a process known as imprinting.
• Imprinting is a process where the DNA in sperm and eggs are modified during
gametogenesis.
• This involved the addition of epigenetic tags that can switch 'on' parts of the DNA
and switch 'off' other parts.
• Different genes are epigenetically silenced in eggs and sperm.
• For most genes, two working copies are inherited, one from each parent.
• With imprinted genes, only one working copy is inherited, due to the differential
silencing of epigenetic tags in sperm and egg development.
• Depending on the gene, either the copy from mother or the copy from father is
epigenetically silenced.
• In sperm development, maternal tags are silenced and in egg development, paternal
tags are silenced.
Imprinting in Tigons and Ligers
• Tigons and ligers are both lion- tiger hybrids produced by interbreeding lions and
tigers.

• Crossing a male tiger with a female lion produces a tigon, which is about the same
size or smaller than either parent.

• Cross between a female tiger and a male lion produces a liger, which is known for its
great size as it is bigger than both lions and tigers.

• The differences can be accounted for by genetic imprinting: tigers and lions imprint
their DNA differently.

• Female lions may mate with multiple males, so a male lion passes on genes that
encourage growth in his own cubs in that litter.
• In contrast, the female lion has evolved imprinted genes that are anti-growth, because
she is equally related to all the potential cubs.
• A female tiger mates with one male, who is equally related to all the cubs.
• The female tiger does not therefore need to evolve anti-growth imprinting ‘defences’.

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 • If a female tiger, with no imprinted defences against paternally inherited genes
encouraging growth in her offspring, is crossed with a male lion, who will contribute
genes that encourage growth, a liger is produced.
• Growth in the liger is a consequence of different patterns of epigenetic and genetic
inheritance in lions and tigers.
• Tigers have a different social structure to lions and are not subject to the same
pressures.

Monozygotic twin studies

• Monozygotic twins are twins who originate from a single fertilised egg, resulting in
genetically identical individuals.
• If the twins are brought up together and share the same environment, they will share
similar overall patterns of epigenetic tags during this time (epigenome).
• As the individuals age and their environments differ, differences in their
environmental factors, such as exposure to pollution, exercise and diet result in
changes in the patterns of epigenetic tags and increasing phenotypic differences.
• Monozygotic twin studies are used to determine whether phenotypic variation is due
to the genetic code of an individual (‘nature’), the environment they were brought
up in (‘nurture’), or a combination of genetic and environmental factors.
External factors impacting the pattern of gene expression
The Effect of oestradiol:
• As a steroid hormone, oestradiol is able to diffuse freely across cell membranes.
• Once inside the cell, oestradiol binds to oestradiol receptors, resulting in a
conformational change and activation.
• Once activated, the hormone–receptor complex can move into the nucleus and bind
to specific sections of DNA located near target genes.
• Once bound, other proteins such as co-regulatory and co-activator proteins are
recruited to the gene, influencing the transcription of the target genes.
• The specific target genes of oestradiol can vary across different tissues and
physiological conditions.
• For example, the genes for follicle-stimulating hormone and luteinising hormone,
genes associated with the development of uterine and breast tissue and genes
involved in maintaining bone health.

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The effect of Lactose in bacteria
• An operon is a cluster of genes that share a promoter.
• The lac operon is a cluster of three genes found in bacterial DNA that code for
proteins involved in the digestion of lactose, a disaccharide found in milk.
• The lac operon includes the gene encoding lactase, the enzyme that hydrolyses
lactose, and a lactose membrane transporter.
• In the absence of glucose, bacteria can utilise lactose as an energy source.
• When lactose is absent, the lac repressor binds to a region called the operator,
preventing the attachment of RNA polymerase to the lac operon promoter and
repressing transcription of the gene.
• When lactose is present, it binds to the repressor, detaching it from the promoter
and allowing RNA polymerase to bind and transcribe the lac operon
• This means that the genes will only be expressed when lactose is present in the
environment.