cellular control Flashcards
what is a mutation
a random/spontaneous change to the sequence of bases in DNA
2 types of mutation
gene mutations
chromosome mutations
what is a gene mutation
change to the base sequence of DNA in one gene
what is a chromosome mutation
change to the structure or number of chromosomes
when do gene mutations occur
mostly take place during DNA replication (S phase of cell cycle)
where do most mutations occur
body (somatic) cells therefore not inherited
associated w mitosis
can mutations occur during meiosis
yes; these can be inherited (however chances are low as there is a huge number of sperm cells)
what do mutagens do
increase the chance of a mutation occurring
types of mutagens
physical
chemical
biological agents
physical mutagens examples
ionising radiation e.g. UV, gamma rays, x rays
chemical mutagens examples
delaminating agents (convert cytosine bases into uracil bases) e.g. tobacco smoke
biological agents mutagens examples
e.g. viruses, agents which change structure of chemical bases
types of gene mutation
point (substitution) mutations
insertion or deletion (INDEL) mutations
what is a point mutation
one DNA nucleotide is replaced by another which has a different base
what is an INDEL mutation
cause a frameshift
one or more nucleotide added/removed therefore sequence of amino acids may be different from the point of mutation onwards
types of point mutation
silent mutation
missense mutation
nonsense mutation
what is a silent mutation
has no effect on the primary and therefore secondary and tertiary structure of the protein (amino acid coded for stays the same)
DNA is degenerate so reduces the effect of point mutations
what is a missense mutation
a change in the base triplet sequence that leads to a change in the amino acid sequence
bodily example of a missense mutation
sickle cell anaemia
causes crystallisation of Hb which causes erythrocytes to become sickled so SA:vol ratio decreases and the erythrocytes can block up capillaries and starve organs of O2
what is a nonsense mutation
a point mutation may alter a base triplet so that it becomes a STOP codon/triplet, resulting in a truncated/shortened amino acid sequence with no function so the protein is degraded, resulting in the absence of a protein
bodily example of a nonsense mutation
Duchenne muscular dystrophy (protein dystrophin is not produced so muscle cells waste away)
explain an INDEL mutation
inserting a new gene/extra DNA nucleotides into an existing gene OR deleting sections of DNA nucleotides from an existing gene causes a FRAMESHIFT
frameshift cause the triplets of DNA bases (codons) to become altered
this is because the code is NON-OVERLAPPING (reading frame for RNA polymerase shifts)
this could result in adjacent/nearby genes being switched on/off
functioning genes could become disabled by this frameshift
bodily example of INDEL mutation
thalassaemia
Hb disorder due to frameshifts as a result of deletions
Hb cannot sequester Fe3+ ions … must be removed by metal chelation therapy
possible effects of mutations
neutral
beneficial
harmful
possible neutral effects of mutations
if the mutation is in the non-coding region of the DNA (intron)
if the mutation is silent: although a base triplet has changed, it still codes for the same amino acid and so the protein’s structure is unchanged
if the mutation does cause a change to the structure of the protein and therefore a different characteristic, but the changed characteristic gives no particular advantage or disadvantage to the organisms e.g. ability to smell honeysuckle, presence of ear lobes
example of possible beneficial effect of a mutation
ability to digest lactose: many mammals cease to be able to digest lactose after infancy so this ability allows an organism to break lactose down into glucose and galactose, which can be used as respiratory substrate
prevents starvation and reduces chances of osteoporosis
examples of possible harmful effects of mutations
phenylketonuria (caused by a substitution mutation in a gene encoding an enzyme involved in phenylalanine conversion i.e. transamination doesn’t occur. if She allowed to build up, it causes brain damage)
Duchenne muscular dystrophy (defected geen encoding dystrophin protein so muscle wastes away)
what does a chromosome mutation affect
the whole chromosome, or number of chromosomes within a cell
what are chromosome mutations caused by and when do they occur
mutagens
normally occur during meiosis so often lead to developmental abnormalities
types of chromosome mutation
duplication
deletion
inversion
translocation
what can duplication as a chromosome mutation lead to?
over-expression of a gene
may affect metabolism
suppression drugs needed
what can deletion as a chromosome mutation lead to?
absence of a gene (could be fatal e.g. if developmental or regulatory)
if codes for enzyme/hormone, may be dangerous
what can inversion or translocation as a chromosome mutation lead to?
all genes still present BUT may inhibit/disable expression of other genes around them
types of transcriptional level regulation
regulation of gene expression in prokaryotes (lac operon)
regulation of gene expression in eukaryotes (chromatin remodelling, histone modification, transcription factors)
bacterial DNA
where are genes controlling related functions located
one circular chromosome and plasmids
located together to form operons
what is an operon
a cluster of genes controlled by a single promoter region
what is the lac operon
E.coli normally metabolises glucose as a respiratory substrate, but if glucose is absent and the disaccharide lactose is present, lactose induces the production of 2 enzymes: lactose permease (lacY) and beta galactosidase (lacZ)
what does lactose permease do
gene encodes channel proteins specific to lactose, which are inserted into bacterial plasma membrane
what does B galactosidase do
breaks glycosidic bond between glucose and B galactose
glucose and B galactose can then be used as respiratory substrates
length of lac operon
consists of a length of DNA about 6000 base pairs
parts of lac operon
lac I gene
promoter region
lac O (operator region: not DNA but does not encode a protein)
lac Z
lac Y
what does lac I gene do
codes for a repressor protein
what is the promoter region
where RNA polymerase binds to initiate transcription
what is the operator region
repressor protein binds here (when operon switched off)
lac Z function
codes for B galactosidase
lac Y function
codes for lactose permease
describe what happens when the lac operon is switched OFF (ie at high glucose concentrations)
lactose absent
repressor protein is constantly produced, and it binds to the operator region
this prevents RNA polymerase binding to the promoter , so the lactose-utilisation genes are not expressed
describe what happens when the lac operon is switched on/induced (ie absence of glucose)
lactose (inducer) binds to repressor protein and changes its shape so it is inactive and cannot bind to operator region
RNA polymerase can bind to promoter region and transcribe lacZ and lacY genes
translated, folded and modified to become enzymes
what does regulation of gene expression in eukaryotes involve
epigenetics
what is epigenetics
control of gene expression through modification of the DNA structure and histone structure
GENES CAN BE SWITCHED ON/OFF
examples of mechanisms that can affect the transcription of genes
chromatin remodelling
histone modification
trancrisption factors
2 forms of chromatin
euchromatin: loosely wound, cells in interphase have this
heterochromatin: tightly wound, cells in meiosis/mitosis have this
describe chromatin remodelling
normally, DNA is tightly coiled around histone proteins (forming chromatin)
during DNA purification, histones need to be broken down to allow access to DNA
this can be done using protease enzymes
euchromatin formed, which RNA polymerase can bind to promoter regions on to cause gene expression
describe histone modification of euchromatin
reduces the positive charge on the histones
DNA coils less tightly around the histones
certain genes can be expressed
describe histone modification of heterochromatin
histones become more hydrophobic so they bind more tightly to each other
DNA was more tightly around histones
cell could be undergoing cell division (promoter region inaccessible for RNA polymerase)
what are transcription factors
proteins that act within the cells nucleus (involved in transcription) to control which genes in a cell are switched on/off
transcription factors mechanism
slide along part of a DNA molecule seeking out the correct promoter region that they are specific to
transcription factors role
may aid or inhibit the attachment of RNA polymerase to DNA and either activate or prevent the transcription of that gene
some are involved in regulating cell cycle checkpoints (G1/S, G2/M, metaphase) or synthesis of proteins in G1 and G2
tumour suppressor genes and porto-oncogenes regulate cell division and mutations in these genes could lead to uncontrolled cell division
REGULATE GENE EXPRESSION
what percentage of human genome encodes transcription factors
8%
what is the benefit of a repressor being continuously produced
organism doesn’t need to expend energy transcribing/translating genes if substrate is unavailable
this conserves ATP
why does E.coli have polycistronic messages? (mRNA that encodes several proteins)
allows transcription of several genes at the same time using a single promoter
in metabolic processes, multiple proteins may be required at the same time
describe mechanism of cAMP as a second messenger
binding of 1st messenger to specific receptor on plasma membrane activates a G protein
adenylyl cyclase activated
ATP converted into cyclic AMP
cAMP activates PKA which activates proteins by phosphorylating them
describe the role of cAMP in activating enzymes
role as 2nd messenger in cells
activates PKA which phosphorylates enzymes
explain why a piece of mRNA is shorter than the gene from which it was transcribed
because the product of gene transcription is the precursor pre-mRNA which contains non-coding sections called introns
these introns are not present in mRNA because they are removed by splicing, and the exons either side of them are lined together using ligase enzyme
explain why molecules such as adrenaline cannot directly enter a cell
they are hydrophilic (not lipid soluble) so cannot diffuse across the phospholipid bilayer due to the hydrophobic fatty acid tails
large
need specific carrier/channel protein or glycoprotein receptor
ATP vs cAMP structure
ATP: 3 phosphate groups, contains phosphoanyrhide bonds, phosphate bonded to ribose (phosphoester bond)
cAMP: one phosphate group, phosphate bonded to ribose (phosphodiester bond)
BOTH have ribose sugar and adenine base
homeotic genes definition
large ancient group of genes involved in controlling development of body plan (ensures body parts develop in the correct positions)
homeobox genes/sequences
a stretch of 180 DNA base pairs (excluding introns)
code for a 60 amino acid sequence (homeodomain)
what’s a homeodomain
60 amino acid sequence
coded for by homeobox genes
act as transcription factors, which activate or repress certain genes
are homeobox genes conserved
very similar
highly conserved between animals, plants and fungi
what do mutations in homeobox genes lead to?
organisms that are not viable (mutations are fatal)
OR could leas to an organism born with deformities which would eliminate it by natural selection
what are hox genes
a subset of homeobox genes which are only found in animals
are hox genes homeobox genes
all hox genes are homeobox genes
not all homeobox genes are hox genes
what do hox genes do in animals
regulate body plan development along the head-tail axis (controls which body parts grow where)
example of hox genes in fruit flies
could result in body parts growing where they should not so organisms may be selected against
hierarchy of homeobox stuff
homeotic genes
|
homeobox genes
|
hox genes
|
homeodomain sequence
describe the role of homeobox genes in the development of eukaryotic organisms
homeobox genes are sequences of 180 DNA base pairs which code for transcription factors of 60 amino acids in length
homeobox genes are expressed in order along the head-tail axis in early embryonic development, and ensure body parts develop in the correct positions
if homeobox genes mutate, this could be lethal for an organism, or body parts may develop in incorrect positions
mitosis definition
cell division regulated with the help of Hox genes
apoptosis definition
programmed cell death
in the context of body plan development: it ensures organs/tissues are correct shapes
also involved in ‘dampening down’ the immune response w help of Treg cells
describe process of apoptosis
- cell held together by cytoskeleton proteins (microtubules, microfilaments and intermediate fibres)
- enzymes (caspases) digest cytoskeleton proteins and the cell deforms. blebs form and chromatin condenses
- cell splits into membrane-bound vesicles (apoptotic bodies). these are engulfed by a phagocyte and digested
apoptosis function in limb development
causes digits to separate from each other
how does apoptosis separate digits
morphogenetic apoptosis acting as a stone sculptor
elimination of material by apoptosis
new shape revealed
what is syndactyly
incomplete separation of digits
what is polydactyly
too many digits
describe control of apoptosis
Hox genes encode transcription factors ( cause production of cell signalling molecules leading to apoptosis)
there are many different cell signalling cascades which result in apoptosis (e.g. death of effector cells in immune response, sculpting of digits in foetal development)
describe changes in rates of apoptosis and mitosis through life
in early life up to end of puberty, rate of mitosis>rate of apoptosis
large parts of adulthood: rate of mitosis and apoptosis are relatively similar
as age progresses, rate of apoptosis>rate of mitosis
explain why the process of apoptosis does not damage nearby cells
no hydrolytic enzymes are released bc contained within the phagocyte
why should the rate of apoptosis in an adult equal the rate of mitosis
adults not growing
too much apoptosis leads to cell loss/degradation
too little apoptosis leads to tumour formation
describe examples of apoptosis in an organisms development
separation of digits to form fingers/toes on hands/feet during limb development
destruction of immune cells
shaping organs/tissues
connections between neurones
outline difference between apoptosis and necrosis
apoptosis= cell fragments isolated in vesicles and digested. no enzymes released outside cell
necrosis= uncontrolled cell death as a result of enzymes being released outside of cell
