Questions on homeobox genes, Hox genes and apoptosis

Question 1

Describe the changes that take place in a cell during apoptosis, in the order in which they occur.

Accepted Answer

B1 enzymes break down the cytoskeleton, so the cell shrinks and the cytoplasm becomes dense with closely packed organelles B1 the chromatin condenses, the nuclear envelope breaks down and the DNA is cut into fragments B1 the cell surface membrane blebs, bulging outwards without breaking, and the cell separates into apoptotic bodies each wrapped in membrane B1 the apoptotic bodies are engulfed by phagocytosis and their contents are digested and reused

Question 2

A homeobox of 180 base pairs lies within a gene 1200 base pairs long. Calculate the number of amino acids in the homeodomain, and the percentage of the gene that the homeobox occupies.

Accepted Answer

M1 three bases code for one amino acid, so divide 180 by 3 A1 60 amino acids M1 180 divided by 1200, multiplied by 100 A1 15 per cent

Question 3

In a fly carrying a mutation in the gene Antennapedia, a pair of legs grows on the head where the antennae should be, and the legs are complete and normally formed. Explain what this shows about how homeotic mutations work, and explain why this is called a homeotic mutation rather than a loss of a structure.

Accepted Answer

B1 the legs are complete and normally formed, so the genes that build a leg are intact and functioning correctly B1 what has changed is where those leg-building genes are expressed: they are switched on in the head region, where antennae should form, as well as in the thorax B1 this shows that a Hox gene's role is to specify the identity of a region, activating the developmental programme appropriate to it, rather than to build any structure directly B1 it is called a homeotic mutation because one region develops with the identity of another region, rather than because any structure has been lost or deleted

Question 4

Explain why a mutation in a single homeobox gene can alter the development of a whole region of an animal.

Accepted Answer

B1 the homeodomain binds to DNA, so the protein coded for by a homeobox gene is a transcription factor B1 it controls the transcription of many other genes, and those genes are the ones that build the structures of the region B1 a change to the transcription factor therefore changes which set of genes is switched on in every cell of that region, so the region can develop with the identity of a different region

Question 5

Compare the events of apoptosis with the events of necrosis in a tissue.

Accepted Answer

B1 a cell undergoing apoptosis shrinks, whereas a cell undergoing necrosis swells B1 in apoptosis the cell surface membrane stays intact and wraps every fragment, whereas in necrosis the membrane breaks and the cell contents escape B1 apoptosis is controlled by signals and by the cell's own enzymes and causes no inflammation, whereas necrosis follows injury or a shortage of oxygen or nutrients and damages neighbouring cells, causing inflammation

Question 6

The hand of a human embryo is at first a flat plate of tissue with no separate fingers. Explain how mitosis and apoptosis together produce five separate digits.

Accepted Answer

B1 mitosis produces the cells of the whole hand plate, including the tissue lying between the developing digits B1 the cells of the tissue between the digits receive a signal and undergo apoptosis, and the apoptotic bodies are removed by phagocytosis B1 the five digits are left free of one another; the number of digits is unchanged, because it is the webbing between them that is removed

Question 7

Cells in some tumours fail to undergo apoptosis even though their DNA is damaged. Suggest how this failure contributes to the growth of the tumour.

Accepted Answer

B1 a cell with DNA damage that cannot be repaired is normally removed by apoptosis, so that the damage is not passed on B1 if apoptosis does not happen the damaged cell survives and continues through the cell cycle, and its daughter cells inherit the damage B1 further mutations accumulate in those descendants, the rate of division exceeds the rate of cell death, and a mass of cells builds up

Question 8

A homeobox gene from a mouse can be inserted into a fruit fly embryo and successfully carry out the fly gene's own job, even though the two species' ancestors diverged over five hundred million years ago. Suggest what this shows about the two species, and suggest why so few changes to the protein this gene codes for have been passed on over that time.

Accepted Answer

B1 it shows that the two species inherited the homeobox sequence from a shared common ancestor that already possessed it B1 it shows the sequence and its function have been conserved across an enormous span of evolutionary time, since a fly protein and its distant mammalian relative can still substitute for one another B1 almost any mutation to a sequence this central to development is likely to be harmful, so individuals carrying it are strongly selected against and the mutation is rarely passed on

Question 9

Withdrawal of a growth factor from a cell can trigger apoptosis just as effectively as delivery of a cytokine can. Explain how a signal from outside a cell and a signal from inside a cell can both lead to apoptosis, giving one example of each.

Accepted Answer

B1 external signals include cytokines released by cells of the immune system, hormones, growth factors and nitric oxide, and either the delivery of one of these or, for a growth factor, its withdrawal can initiate apoptosis B1 internal signals arise from the cell's own condition, and the example to give is DNA damage that the cell's repair systems cannot correct B1 both kinds of signal converge on activating the same enzymes, which then carry out the same ordered sequence of apoptosis regardless of which signal started it

Question 10

Outline how a failure of apoptosis between the developing digits can result in a baby being born with fingers joined by a web of skin, a condition called syndactyly.

Accepted Answer

B1 the tissue between the developing digits is normally removed by apoptosis, in strips, as the hand plate takes shape B1 if the cells of that tissue do not receive, or cannot respond to, the signal to undergo apoptosis, they are not removed and remain in place B1 the digits themselves have formed normally and are present in the correct number; only the removal of the tissue joining them has failed

Question 11

In a healthy adult, apoptosis removes cells at a rate of the order of ten thousand million cells a day, and mitosis replaces them at a matching rate. Calculate the approximate number of cells replaced in one year, and give your answer in standard form to two significant figures.

Accepted Answer

M1 number per year = number per day × 365 M1 1 × 10¹⁰ × 365 A1 3.7 × 10¹² cells replaced in a year (3.65 × 10¹² unrounded)

Question 12

Compare the consequence of too little apoptosis in a cell with damaged DNA with the consequence of too much apoptosis in neurones, referring to a named condition each can lead to.

Accepted Answer

B1 too little apoptosis lets a cell with DNA damage it cannot repair go on dividing, whereas too much apoptosis destroys cells, such as neurones, that are healthy and often cannot be replaced B1 too little apoptosis, combined with unchecked division, is one route to a tumour building up from the damaged cell's descendants, whereas too much apoptosis of neurones contributes to neurodegenerative disease and to the tissue damage seen around a stroke B1 both show that apoptosis must be matched to mitosis: neither too little nor too much keeps a tissue at a stable, healthy size

Question 13

State the length of a homeobox in base pairs, and the length in amino acids of the homeodomain it codes for.

Accepted Answer

B1 the homeobox is 180 base pairs long B1 the homeodomain is 60 amino acids long, because three bases code for one amino acid

Question 14

State what colinearity means in a Hox gene cluster, and state how many Hox gene clusters a human has.

Accepted Answer

B1 colinearity is the match between the order of the Hox genes along the chromosome and the order of the body regions they specify, from head to tail B1 a human has four Hox gene clusters, on four different chromosomes

Question 15

State the name of the gene whose protein product halts the cell cycle at a checkpoint and triggers apoptosis when DNA damage cannot be repaired, and state what type of gene this is.

Accepted Answer

B1 the gene is p53 B1 it is a tumour suppressor gene