6.1.1 Cellular Control

Question 1

What is a mutation?

Answer 1

• a random change to the DNA
• they may occur spontaneously during DNA replication before cell division
• some chemicals may be mutagenic and increase chances of mutation

Question 2

What is somatic mutations?

Answer 2

• mutation associated with mitotic division
• are not passed down to offspring
• may be associated with the development of cancerous tumours

Question 3

How might mutations be inherited by offspring?

Answer 3

• mutations associated with meiosis and gamete formation

Question 4

What are the two main classes of DNA mutation?

Answer 4

• point mutation: one base pair substitutes another
• insertion or deletion (indel) mutation: one or more nucleotides are inserted or deleted from a length of DNA
• these may cause a frameshift

Question 5

Where do point mutations occur?

Answer 5

• the mRNA as codons, that was transcribed
• complementary to the base triplets on the template strand of the length of DNA

Question 6

What are the three types of point mutation?

Answer 6

• silent
• missense
• nonsense

Question 7

Describe silent mutations

Answer 7

• a silent mutation is a point mutation involving a change to the base triplet, where the triplet still codes for the same amino acid
• this is because all amino acids, apart from methionine, have more than one base triplet code
• this reduces the effect of point mutations
• the primary structure of the protein, and so the secondary and tertiary structure is not altered

Question 8

Describe missense mutations

Answer 8

• a change to the base triplet sequence that leads to a change in the amino acid sequence in a protein
• this may have a significant effect on the protein produced
• the change to primary structure changes the secondary etc
• this prevents it from carrying out its usual function
• sickle cell anaemia results from a missense mutation

Question 9

Describe nonsense mutations

Answer 9

• a point mutation may alter a base triplet so that it becomes a termination triplet
• this results in a truncated protein that will not function
• it will most likely be degraded within the cell
• Duchenne muscular dystrophy is the result of a nonsense mutation

Question 10

How do insertions and deletions cause frameshifts?

Answer 10

• if nucleotide base pairs, not in multiples of three, are inserted in the gene or deleted from the gene, all the subsequent base triplets are altered
• this is a frameshift
• this is because the code is non-overlapping and read in groups of three bases
• when the mRNA is translated, the amino acid sequence is severely disrupted
• hence the primary structure and the tertiary structure is much altered
• protein cannot carry out its normal function
• if it is very abnormal, it will be rapidly degraded within the cell
• some forms of thalassaemia are caused by frameshifts

Question 11

Why are insertions or deletions of a triplet of base pairs not cause a frameshift?

Answer 11

• since it is a triplet, it will either result in the addition or loss of an amino acid

Question 12

What are expanding triplet nucleotide repeats?

Answer 12

• some genes contain a repeating triplet such as CAG CAG CAG
• in an expanding triple nucleotide repeat, the number of CAG triplets increase at meiosis and again from generation to generation
• Huntingdon disease results from this
• they will develop symptoms if the number of repeating sequences go above a certain number

Question 13

Why are not all mutations harmful?

Answer 13

• many mutations are beneficial and have helped to drive evolution through natural selection
• different alleles of a particular gene are produced via mutation

Question 14

Give some examples of beneficial and neutral human mutations

Answer 14

• blue eyes arose 6000-8000 years ago
• allows people to see better is less bright light
• paler skin allows better vitamin D absorption in lower light

Neutral mutations:

• inability to smell certain flowers
• differently shaped ear lobes

Question 15

Describe how E.coli uses respiratory substrates

Answer 15

• the bacterium E.coli normally metabolises glucose as repiratory substrate
• however, if glucose is absent and the disaccharide lactose is present, lactose induces the production of two enzymes:
• lactose permease: allows lactose to enter the bacterial cell
• ß-galactosidase: hydrolyses lactose to glucose and galactose

Question 16

Describe the lac operon

Answer 16

• consists of a length of DNA, about 6000 base pairs long
• contains an operator region lacO next to structural genes lacZ and lacY, which code for beta-galactosidase and lactose permease, respectively
• next to lacO is the promoter region, P, which the enzyme RNA polymerase binds to begin transcription of the structural genes lacZ, lacY
• -* operator region and promoter regions are the control sites
• the regulatory gene, I, codes for a repressor protein (LacI)
• when this gene is expressed, the repressor protein binds to the operator, preventing RNA polymerase from binding to the promoter region
• so, lacZ and lacY are not transcribed, so enzymes for lactose metabolism are not made

Question 17

Describe how the lac operon works

Answer 17

• lactose molecules bind to the LacI repressor protein molecules
• this alters the shape of the LacI repressor protein, preventing it from binding to the operator
• the RNA polymerase enzymes then binds to the promoter regions and begins transcribing the structural genes into mRNA that will then be translated into the two enzymes

Question 18

What are transcription factors?

Answer 18

• proteins or short non-coding pieces of RNA, that act within a eukaryotic cell’s nucleus to control which genes in a cell are on or off
• they slide along a part of the DNA molecule, seeking and binding to their specific promoter regions
• may aid or inhibit the attachment of RNA to the DNA and activate or suppress transcription of the gene
• about 8% of genes encode transcription factors
• many genes have their promoter regions far away, but since DNA can bend, it may not spatially be far away

Question 19

Why are transcription factors necessary in eukaryotic cells and examples?

Answer 19

• they are essential for the regulation of gene expression, making sure different genes are activated or suppressed in different cells
  e. g.
• regulating the cell cycle
• tumpur suppressor genes
• proto-oncogenes

Question 20

How is gene expression regulated at the transcriptional level in prokaryotes and eukaryotes?

Answer 20

Prokaryotes:

• enzymes that may only be needed under specific conditions are synthesised at varying rates, according to the needs of the cell
• e.g. lac operon

Eukaryotes:

• transcription factors

Question 21

How is does gene regulation occur post-transcription?

Answer 21

• introns and exons

Question 22

Describe how introns and exons work

Answer 22

• all the DNA of a gene, both introns and exons, is transcribed
• the resulting mRNA is primary mRNA
• it is then edited and the RNA introns are removed
• the remaining mRNA exons, corresponding to DNA exons, are joined together
• endonuclease enzyme may be involved in the editing and splicing processes
• some introns may themselves encode proteins
• some become short non-coding lengths of RNA involved in gene regulation

Question 23

How does post-translational level of gene regulation occur?

Answer 23

• post-translational regulation of gene expression involves the activation of proteins
• many enzymes are activated by being phosphorylated

Question 24

Describe how cyclic AMP is used to activate proteins in post-translational gene expression

Answer 24

1. a signalling molecule, such as glucagon, binds to a receptor on the plasma membrane of a target cell
2. this activated a transmembrane protein which then activates a G protein
3. the activated G protein-activated adenyl cyclase enzymes
4. activated adenyl cyclase enzymes catalyse the formation of many molecules of cAMP from ATP
5. cAMP activates PKA (protein kinase A)
6. activated PKA catalyses the phosphorylation of various proteins, hydrolysis ATP in the process
   - this activates many enzymes in the cytoplasm, e.g. convert glycogen to glucose
7. PKA may phosphorylate another protein (CREB, cAMP response element binding)
8. this then enters the nucleus and acts as a transcription factor to regulate transcription

Question 25

What are homeobox sequences and describe its structure?

Answer 25

- a sequence of 180 base pairs (excluding introns) found within genes that are involved in regulating patterns f anatomical development in animals, fungi and plants - sometimes called the homeobox genes - it encodes a 60-amino acid sequence, called a homeodomain sequence, within a protein - this can fold into a particular shape and bind to DNA, regulating the transcription of adjacent genes - these proteins are transcription factors and act within the cell nucleus - these homeodomain-containing proteins fold into a shape called H-T-H - it consists of two alpha helices connected by one turn - part of the homeodomain amino acid sequences recognises the TAAT sequences of the enhancer region of a gene to be transcribed

Question 26

What is the difference between homoeobox and Hox genes?

Answer 26

- Hox genes are only found in animals - homeobox genes are found in animals, plants and fungi

Question 27

What are two features of homeobox gene sequences?

Answer 27

- they are very similar between different species - these genes are highly conserved: as they first arose in an early ancestor

Question 28

How do Hox genes control body plan development in animals?

Answer 28

- the Hox genes regulate the development of embryos along the anterior-posterior axis - they control which body parts grow where - mutations cause parts to grow in wrong places

Question 29

How are Hox genes arranged in clusters?

Answer 29

- they are arranged in clusters and each cluster may contain up to 10 genes - in tetrapods, there are four clusters - at some point during evolution, the Hox clusters have been duplicated

Question 30

Explain how Hox genes work

Answer 30

- Hox genes are active in early embryonic development - they are expressed in order along the anterior- posterior axis of the developing embryo - the sequence and order of the gene expressions correspond to the sequences and timing of the development of body parts, which is called colinearity - these genes may encode homeodomain proteins that act in the nucleus as transcription factors - they can switch on cascades of activation of other genes that promote mitotic cell division, apoptosis, cell migration and help regulate the cell cycle - Hox genes are similar across different classes of anima;s - a fly can function with a chicken Hox gene

Question 31

How are Hox genes regulated?

Answer 31

- Hox genes are regulated by other genes called gap genes and pair-rule genes - in turn, these genes are regulated by maternally supplied mRNA from the egg cytoplasm

Question 32

What is the Hayflick constant?

Answer 32

- normal body cells divide by mitosis a limited number of times before dying - around 50 times

Question 33

What is apoptosis?

Answer 33

- programmed cell death - different from cell death due to trauma, which involves hydrolytic enzymes

Question 34

Describe the process of apoptosis

Answer 34

1. enzymes break down the cell cytoskeleton 2. cytoplasm becomes dense with tightly packed organelles 3. cell surface membrane changes and small protrusion called blebs form 4. chromatin condenses, the nuclear envelope break and DNA breaks into fragments 5. the cell breaks into vesicles that are ingested by phagocytic cells so that cell debris does not damage any other cells or tissues. the process happens quickly

Question 35

Describe how apoptosis is controlled

Answer 35

- many cell signals control apoptosis - some may be released by cells when genes that are involved in regulating the cell cycle and apoptosis respond to internal cell stimuli and external stimuli, such as stress - these signalling molecules include, cytokines, hormones, growth factors and nitric oxide - nitric oxide induces apoptosis by making the inner mitochondrial membrane more permeable to hydrogen ions and dissipating the proton gradient - proteins are rleased into the cytoplasm where they bind to apoptosis inhibitor proteins, allowing apoptosis to occur

Question 36

How is apoptosis integral to plant and animal tissue development?

Answer 36

- extensive proliferation of cell types is prevented by pruning through apoptosis, without any hydrolytic enzymes that could damage surrounding tissues - during limb development, apoptosis causes digits to separate from each other - apoptosis removed ineffective or harmful T-lymphocytes during the development of the immune system - children apoptose 20-30 billion cells per day, adults, 50-70 million cells per day - rate of cells dying should equal rate of cell produced by mitosis: - not enough apoptosis leads to tumour formation - too much apoptosis leads to cell loss and degeneration - cell signalling plays a big role in maintaining right balance