A LEVEL: Biology (F215), Cellular Control

Ginny.T

Biology 2

Cellular Control: Unit

What is a gene?

• A length of DNA that codes for polypeptides 
• In a human genome there are nearly 25,000 genes.
• Found on the linear chromosomes
• Each gene occupies a specific place
• A gene is part of the DNA
• Associated with histone proteins 

The Genetic Code

The sequence of nucleotide bases on a gene provides a code for a polypeptide or protein

• Triplet Base Code
• Four bases arranged in a group of three, so 4cube is 64, we only need 20 amino acids for protein synthesis
• Degenerate code, as there are many different codes for producing one type of polypeptide
• Not a universal code

How does the nucleotide sequence code for the amino acid sequence in a polypeptide?

mRNA travels via the pores in the nucleus to the Ribosomes on the RER to be translated. 

* the creation of a single stranded mRNA copy of the DNA coding strand.

TRANSLATION - The assembly of polypeptides (proteins) at ribosomes

 

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Transfer RNA

1. Made in the nucleus
2. Passed into the cytoplasm
3. folded into shape - RNA
4. Three exposed bases at the end = amino acid binding site
5. Three unpaired nucleotide bases = anticodon
6. Anticodon = Binds with = Complementary Codon

POLYPEPTIDE: THE ASSEMBLY

1. Molecule of RNA binds to a Ribosome

2 codons (6 bases) attach to a ribosome subunit. exposed to the big one and the first codon is always AUG - ATP and an enzyme, a tRNA with methionine and the anticodon UAC forms hydrogen bonds with the codon.

2. Second tRNA binding

A second tRNA, with a different amino acid binds to the exposed codon with the complementary anticodon. 

3.

A peptide bond forms between the two amino acids. An enzyme in the ribosomal unit is what catalyses the reaction.

4.

Ribosome is able to move along the mRNA, reading the rest of the codon. A third tRNA brings on another amino acid, and a peptide bond forms, then dipeptide. The first then moves along to bring another of its amino acid.

5.

Polypeptide chain grows until a stop codon is reached. No corresponding tRNA for these codons:

• UAA
• UAC
• UGA

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MUTATIONS

Mutation - Change in the amount of, or arrangement of, the genetic material in a cell. 

Chromosome Mutations - Involve changes to part of or whole chromosomes.

DNA Mutations - Are changes to genes due to changes in nucleotide base sequences. 

This random change to the genetic material, may be due to:

• base deletion
• base insertion
• base substitution

Chromosome Mutations involves a change in the structure of a chromosome, such as:

• deletion
• inversion
• translocation

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MUTATIONS MAY OCCUR DURING DNA REPLICATION.

DNA Mutations

mutations during mitosis is called a somatic mutation - 

PROS - not passed on to offsprings

CONS - contributes to ageing process & cancer

Two classes of DNA mutations:

1. Point mutations: one base pair replaces another, this is called a substitution

2. Insertion/deletion mutations: one or more nucleotide pairs are inserted or deleted from a length of DNA. These cause a frameshift.

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Genetic diseases that are the result of DNA mutations:

• Cystic Fibrosis 

Mutation: deletion of a triplet of base pairs, deleting an amino acid

• Sickle-cell Anaemia

Mutation: In a point mutation on codon 6 of the gene on a beta polypeptide chains of haemoglobin. Amino acid, Valine replaces Glutamic acid.

• Cancer/dividing cells

Mutation: Growth-promoting regulation genes = Prootoncogenes, 

                 Unregulated-cell division genes= Oncogenes

Mutation that changes prootoncogenes which alters the ability of the prootoncogenes and          instead forms oncogenes which does not regulate cell division. This can lead to the formation of tumours.

• Huntington Diseases

Mutation: An expanded triple nucleotide repeat = a stutter

Normal gene for the disease has a repeating CAG sequence, if this reaches above threshold value, the protein is altered enough to cause Huntington disease - manifest later in life such as dementia and loss of motor control. 

Allele - an alternative version of a gene. It is still at the same locus on the chromosome and codes for the same polypeptide but the alteration to the DNA base sequence may alter the protein’s structure. 

when a gene is altered by a change to its base sequence, it becomes another version of the same gene. It is an allele.

A change to an allele has no effect if:

• the mutation is in a non-coding region of the DNA
• it is a silent mutation, the change in the three base sequence still codes for the same amino acid. 

This means that it is neutral, as it offers no advantage or disadvantage.

Mutations with Harmful or Beneficial Effects

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The lac operon 

E.coli bacterium - codes for 3000 proteins, and can switch on or off a gene based on its environment 

It can use lactose as a respiratory substrate and any inducible enzymes would be synthesised at a varying rate, depending on the medium. 

LACTOSE ABSENT MEDIUM of e.coli could be placed into LACTOSE PRESENT MEDIUM.

1. Lactose is not metabolised
2. Enzymes are not available to metabolise the lactose.
3. The enzymes are β-galactosidase (catalyses hydrolysis of lactose: glucose and galactosidase) and lactose permease (transports lactose into the cell)
4. Lactose triggers the production of the two enzymes - inducer 

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How the lac operon works:

when lactose is absent from the growth medium: 

1. The regulator gene (I) is expressed, this synthesises the repressor protein has two binding sites:

• Lactose
• Operator region

1. Repressor protein binds to the operator region, obscuring the path and space for the RNA polymerase to bind to the promoter region.
2. RNA polymerase cannot bind and therefore cannot induce a production of the mRNA to  transcribe the structural genes.
3. No genes are translated and enzymes are not synthesised. 

when lactose is present in the growth medium:

1. The lactose inducer binds to the other binding site on the repressor protein.
2. changing the shape of the protein
3. meaning it cannot bind to the operator region
4. the repressor disassociates from the operator region
5. the promoter region is unblocked
6. RNA polymerase can now bind and begin to transcribe for the structural genes and into β-galactosidase (Z) and lactose permease (Y)
7. The lactose permease allows more lactose to enter into the cell and the β-galactosidase allows that lactose to be metabolised into glucose and galactose.
8. sugars can be used for respiration, and thus gains energy from lactose.

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GENES AND BODY PLANS 

Example used: Drosophila

why?

• incredibly fast DNA replication

1. No new cell membrane - multinucleate syncytium is formed
2. after 8th division the nuclei migrate to the outer party around a yolky substance.
3. Division rate slows, after 14th division. Transcription begins and replications slows down.
4. Plasma membrane invaginate and forms a single outer layer.
5. 2-3 hours, it divides into segments - corresponding to the body plan

Genetic Control

Development is mediated by homeobox genes.

maternal effect genes —> determine embryo polarity.

segmentation genes —> specifies the polarity of each gene

homeotic selector genes —> specify the identity of each segment - directs it to the development of specific individual body segments.

two gene families:X

1. complex that regulates development of the thorax & abdomen segments
2. complex that regulates development of head and thorax segments.

GENETIC CONTROL OF DEVELOPMENT IN OTHER ORGANISMS

Homeobox genes: control the development of the body plan of an organism, including the polarity and positioning of the organs.

the genes contain a sequence of 180 base pairs - 60 polypeptides. 

some are transcription factors

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APOPTOSIS (Programmed cell death)

Cells can undergo 50 cell divisions (Hayflick constant)

During apoptosis: tidy cell death via a chain of biochemical events. 

CONTRASTS with - untidy cell death, cell necrosis that leads to the release of hydrolytic enzymes.

CONTROL

• diverse range of cell signals
• cytokines made by the cells of immune systems
• hormones, growth factors and nitric acid

Nitric acid can induce apoptosis - makes the mitochondrial membrane more permeable to hydrogen ions and dissipating the proton gradient.

APOPTOSIS AND DEVELOPMENT

required for the development of body parts.  

mitosis and differentiation creates the bulk of body parts - apoptosis refines the parts by removing unwanted structures. 

• not enough apoptosis can lead to the formation of tumours
• too much leads to cell loss and degeneration. 

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MEIOSIS

A reduction division. The resulting daughter cells have half the original number of chromosomes. They are haploid and can be used for sexual reproduction.  

Pee on the M A T

MEIOSIS I

Prophase 1 

• chromatin condenses and undergoes supercoiling.
• chromosomes shorten and thicken
• are now visible
• chromosomes form homologous pairs
• one maternal and one paternal
• non-sister chromatids wrap and attach at points called chiasmata
• they swap sections of chromatids = crossing over
• nucleolus disappears and nuclear envelope disintegrates
• spindles form made out of protein microtubules
• prophase I lasts for days-years depending on the species.

Metaphase I

• bivalents lineup across the equator, a spindle fibre attached to the centromeres, the chiasmata are still present
• bivalents arranged randomly
• the member of the homologous pair facing opposite ends
• so the chromosomes segregate independently when they’re pulled apart.

Anaphase I

• homologous chromosomes in each bivalent are torn apart or pulled away by spindle fibres to opposite poles
• Centromeres do not divide
• chiasmata separate, lengths of DNA that have been crossed over remain with the chromatic and become attached. 

Telophase I

• Two nuclear envelopes form, one around each set of chromosome, cell divides by cytokinesis, brief interphase and chromosomes uncoil.
• in plant cells - straight to meiosis II

MEIOSIS II

Prophase II

• nuclear envelope breaks down again
• nucleolus disappears, chromosomes condense and spindles form

Metaphase II

• chromosomes arrange themselves at the equator. Spindle fibres attach to the centromere. 
• chromatids are randomly assorted.

Anaphase II

• centromeres divide, chromatids are pulled to opposite poles by spindle fibres, chromatids randomly segregate.

Telophase II

• nuclear envelopes reform around the haploid daughter cells
• two cells to give four haploid daughter cells (animals)
• tetrad of four haploid cells are formed (plants)

SIGNIFICANCE OF MEIOSIS

sexual reproduction increases genetic variation. 

During fertilisation two haploid gametes join to produce a zygote that is diploid. 

IMPORTANT TERMS:

Genotype: genetic makeup of the organism  -> what alleles it contains

Phenotype: characteristics expressed in the organism, these can be observed

Homozygous: two identical alleles for a particular gene

Heterozygous: two different alleles of the same gene

Cystic Fibrosis: 

caused by a mutation to the autosomes -> chromosomes not involved with determining the sex, disrupts transport of chloride ions & water to the membranes lining the airways and reproductive tracts - build of mucus, -> mucus dehydrates and bacterial infections can occur. 

heterozygous: CFcf

people with cystic fibrosis are homozygous recessive: cfcf

Dominant & Recessive

dominant: always expressed in the phenotype even when another allele of the same gene is resent

recessive: expressed only when the presence of an identical allele is present in the genotype

Codominant: two alleles of the same gene if they’re both expressed in the phenotype. 

Linkage:

two ore more genes located in the same chromosome, normally inherited together, because they did not segregate individually during meiosis. 

Sex Linkage:

characteristics are sex linked if gene that codes for something is found on the X Y chromosomes. 

USING GENETIC DIAGRAMS

H -> allele for normal factor VIII

h -> allele for non-functioning factor VIII

haemophilia is a recessive inheritance pattern

Parental Genotypes                           Carrier Mother                                       Normal Father

Parental Genomes                                   XᴴXʰ                                                         XᴴY

OFFSPRING GENOTYPES

MALE

GAMETES

FEMALE GAMETES

  Xᴴ

Y

Xᴴ

Xᴴ Xᴴ

normal female

XᴴY

normal male

Xʰ

XᴴXʰ

carrier female

XʰY

haemophilic male

look at page 126-127

Interactions between Gene Loci

Epistasis: Interactions of different gene loci so that one gene locus masks or suppresses the expression of another gene locus. 

• may work against each other - masking
• may work together in a complementary fashion

Working Antagonistically 

When a homozygous gene is recessive but is able to prevent the expression of another allele at another locus. The alleles at the first locus are epistatic to the alleles at the second locus which are described as hypostatic. 

NOT INHERITED —> Based on gene interaction and reduced phenotypic variation. 

GET THIS CHECKED OVER WITH BIO TEACHERS AT SOME POINT (I’ve left space for revision notes)

INTERACTIONS BETWEEN GENE LOCI

Coat colour in mice

Alleles A/a -> found in the mice

allele a —> mutation —> produces a black coat

gene B/b (found at a different locus)—> controls the production of pigment 

individuals with gene B —> produce pigment (dominant gene)

individuals with bb —> cannot produce the pigment —> albino 

Gene B/b                                   Gene A/a  

Precursor substance ——————> black pigment ——————> agouti pattern

     (colourless)

ratio of 9:3:4

OTHER RATIOS: 9:3:3:1

THE CHI-SQUARED (𝒳²) TEST

𝒳² =       ∑(O-E)²

             ————

                    E

𝒳² =     the sum of (observed numbers (O) - expected numbers (E))

        ———————-————————————————————

                                          Expected numbers (E)

CONTINUOUS AND DISCONTINUOUS VARIATION

discontinuous variation: qualitative differences between phenotypes.

                             There are no intermediate categories, clearly distinguishable categories  (gender)

continuous variation: quanititiatve differences between phenotypes.

There are a wide range of variation within a population- no distinct categories (eg. height, weight) 

                                                                                                                                                                                   

In both types of variation, more than one gene may be involved, although in discontinuous variation this may mean that epistasis occurs as one gene may mask or influence the expression of another gene. In most cases of discontinuous variation there may only be one gene -> monogenic. 

In Discontinuous variation:

• different alleles at a single gene locus can have large effects on phenotypic expression
• different gene loci has an effect on the phenotype 
• eg. codominance, dominance and recessive patterns of inheritance

In Continuous variation 

• controlled by two or more genes
• each gene adds something to the phenotype
• different alleles at different locus has a small effect on the phenotype
• po;ygenes -> polygenic, 2 or more genes that contribute to many things unlinked genes 

POLYGENIC GENETICS 

page 138 - 139 

practice papers —> go to teachers

THE ROLES OF GENES AND ENVIRONMENT IN EVOLUTION

Environmental Resistance: created by water availability and territory etc 

they can be both abiotic and biotic. 

EVOLUTION BY NATURAL SELECTION & GENETIC DRIFT

Gene Pool: completely range of alleles present in a population

Allele Frequency: how often an allele occurs in a population

Evolution by Natural Selection

• individuals in a population vary (different alleles)
• new alleles are generated by mutations
• predation, disease and competition (selection pressure) create a struggle for survival
• some are more adapted to the selection pressures
• individuals with a better allele, survive better, reproduce and pass on the beneficial allele
• greater proportion of the next generation inherits the beneficial allele.
• so they also have a better chance of survival, 
• frequency of the beneficial alleles increases every generation. 

Evolution and the Environment

selection in a stable environment

• individuals with characteristics more in the middle of the graph are more likely to survive and reproduce.
• stabilising selection: reduces the range of possible phenotypes
• eventually more organisms will have phenotypes that are more in the middle of the graph, and the result is a taller graph in the average region.