Mutations and Variation Flashcards
Mutation
Change in the sequence of bases in DNA
Ways in which change in sequence can be caused
Substitution
Deletion
Insertion
Point mutation
Only one nucleotide is affected
Substitution
Changes the codon - may still code for the same amino acid (degenerate) ; not changing primary structure
Deletion or insertion
Leads to framsehift mutation ; ,over the reading frame of the sequence of bases (non-overlapping) - changes every successive codon from point of mutation
Effects of different mutations
No effect
Damaging
Beneficial
No effect
No effect on phenotype - proteins still synthesised
Damaging
Proteins no longer synthesised or they are non-functional
Beneficial
Protein is synthesised that adds a new characteristic - people with a certain mutation are immune to infection from HIV
What increases rate of mutation
Mutagens - physical/chemical/biological agent which causes mutations
Examples of mutagens
Free radicals can acts as oxidising agents - changing structure of nucleotides/ionising rays
Delaminating agentsbalter bases
Viral DNA may insert itself into a genome
What is a silent mutation?
They occur in the non-coding regions of DNA - introns - do not change overall structure of protein
Nonsense mutations
Codon becomes a stop codon instead of coding for an amino acid - shortened protein often non functional
Chromosome mutations
Alter the whole chromosome - deletion (break off section of chromosome), duplication (sections get duplicated), translocation (section of one chromosome breaks and joins another non-homologous chromosome) and inversion (section is broken off - reversed - and joins back)
Expressing genes only when products are needed
Prevents vital resources from being wasted
Gene regulation stages
Transcriptional - turned on or off
Post-transcriptional - mRNA modified which regulates translation and types of proteins
Translational - translation can be stopped or started
Post-translational - proteins modified after synthesis which changes their functions
Transcriptional control - heterochromatin
Tightly wound DNA causing chromosomes to be visible during cell division
Euchromatin
Loosely wound DNA present during interphase
How does hetero/euchromatin affect transcription?
Transcription of genes not possible when DNA is tightly wound like with heterochromatin because RNA polymerase cannot access the genes ; genes in euchromatin can be freely transcribed however
How is this example of control?
This regulation ensures proteins necessary for cell division are synthesised in time for mitosis - prevents energy intensive process of protein synthesis while cells are still dividing
Histones
Positively charged
How does histone modification work?
ACETYLATION - REDUCES POSITIVE CHARGE ON HISTONES CAUSING THEM TO COIL LESS TIGHTLY - ALLOWS CERTAIN GENES TO BE TRANSCRIBED
METHYLATION - MAKES HISTONE MORE HYDROPHOBIC SO COIL MORE TIGHTLY - PREVENTS TRANSCRIPTION
Epigenetics
Control of gene expression by modification of DNA
Operon
Group of genes that are under control of same regulatory mechanisms and are expressed at the same time
How are operons efficient?
If certain genes not needed all genes are switched off
If glucose not present….
Lactose is metabolised
Lac operon
Has 3 genes lacZ, lacY, lacA - structural genes used to code for 3 enzymes (B-galatcisodase etc)
What is sequence of structures with lac operon
Regulatory gene (codes for a depressor protein)
Promoter
Operator (what RNA polymerase binds to)
Absence of lactose
Regulator gene codes for depressor protein that prevents transcription of structural genes
Down regulation
Idea of depressor protein binding to operator and preventing RNA polymerase from binding to DNA and beginning transcription
Promoter
Section of DNA that is the binding site for RNA polymerase
When lactose is present
Lactose binds to depressor protein causing it to change shape - no longer binds to operator and as a result RNA polymerase can bind to operator allowing enzymes to be synthesised
Cyclic AMP?
RNA POLYMERASE STILL SLOW RATE OF TRANSCRIPTION that needs to be up regulated to produce the required quantity of enzymes - binding of camp receptor protein RCP (which should be bound to CAMP)
Transport of glucose into bacterial cell
Decreases camp levels reducing transcription of genes responsible for metabolism of lactose
If both glucose and lactose are present
Still be glucose that is metabolised - preferred respiratory substrate
Caps
Pre-mRNA is formed from transcription ; a cap is added to 5’ end and a long chain of adenine nucleotides tail is added to 3’ allowing stabilising of mRNA and preventing degradation in cytoplasm
Post transcriptional control mrna
Splicing occurs where RNA is cut at introns (non coding dna) and exons are joined together within the nucleus - this nucleotide sequence can be edited by addition/deletion of bases - synthesis of many different proteins from a single mrna molecule
Translational control
Degradation of mrna - more resistant molecule = longer it will last in cytoplasm so more of protein made
Initiation factors and inhibitory proteins which aid/prevent binding of mrna to ribosomes
Protein kinases
Catalyse addition of phosphate group to proteins - changes tertiary structure/function of protein - enzymes activated this way
Post translational control
Non protein groups
Modifying amino acids and formation of bonds (disulfide bridges)
Folding/shortening
Modification by camp
Structural vs regulator genes
Structural genes encode proteins required for structural/functional use
Regulatory genes encode factors that control expression of structural genes
Morphogenesis
Regulation of pattern of anatomical development
Drosophila
Small - easy to keep - have a short life cycle
Homeobox genes
Group of genes which all contain a homeboys - section of DNA z that is 180 base pairs long coding for a part of the protein 60 amino acids long that is highly conserved in plants animals and fungi
What is homeodomain
Part of protein that is highly conserved (see homeobox) - binds to DNA and switches other genes on or off thus homeobox = regulatory genes
Hox genes
Group of homeobox genes that are only present in animals - responsible for correct position of body parts
How are hox genes found
In gene clusters - mammals have 4 clusters on different chromosomes
How have hox genes arisen
One notebook gene with accumulated mutations
Hox genes along chromosome
The order in which they appear along the chromosome is the order in which their effects are expressed in the organism
Body plans
Cross section through the organism showing fundamental arrangement of tissue layers
Diploblastic
Two primary tissue layers
Tripoblastic
Three primary tissue layers
Individual vertebrae
All developed from segments in the embryo called somites - directed by hox genes to develop in particular way depending on their position in the sequence
Radial symmetry
No left or right sides only a top and bottom
Bilateral symmetry
Organisms have both left and right sides and a head and tail rather than top and bottom
Asymmetry
Sponges - no lines of symmetry
Shaping body parts
Hox genes regulate both mitosis and apoptosis - role of mitosis is to increase the number of cells leading to growth ; role of apoptosis is to remove unwanted cells and tissues - cells undergoing apoptosis can also release chemical signals which stimulates mitosis and cell proliferation
Factors affecting expression of regulatory genes
Internal factors - change due to the release of hormones/psychological stress
External factors - a change in temperature or intensity of light
Drugs can also affect activity
Thalidomide was given to pregnant women to treat morning sickness ; shortened limbs
Prevents formation of stores of capillaries which are necessary for some tumours to grow and develop
Beneficial mutation
Enhanced function of protein
What happens with amino group after Deamination?
Converted to ammonia to then be excreted from the body
Can be used as a source for Gluconeogenesis
Enter kerbs cycle as pyruvate
Transcriptional control
Heterochromatin vs euchromatin
-> acetylayion/phosphorylation
<- methylation
Post transcriptional control
mRNA splicing (introns and exons) - editing too - many proteins from 1 mRNA
Adenine tail + cap on 5’ prevents degradation in cytoplasm
Translational
Switching translation on or off - degrade mRNA or inhibitory proteins binding to mRNA prevents binding
Upregulate - PHOSPHORYLATION BY PROTEIN KINASES ACTIVATES INITIATION FACTORS
What activates protein kinases
Cyclic AMP
Post translational control
Make it into gylcoprotein - add chains
Protein folding
AMINO ACIDS MODIFIED TO MAKE BONDS
CAMP + CRP - UP REGULATES RNA POLYMERASE/ KINASES
Homeobox genes
Regulatory genes 180 base pairs long that code for a regulatory protein (part of which is called the homeodomain) that helps determine body plans/development
Homeobox genes ARE
Highly conserved in plants animals and fungi
Function of Homeobox genes
Regulate mitosis + apoptosis (hox genes determine this in humans)
Hox genes
4 clusters - highly conserved
