Chapter 19 - Genetics of Living Systems

Types of mutations

• substitution

  • change of a singular nucleotide

  • changes the codon

  • change in primary structure

• deletion

  • leads to a frameshift mutation

  • shifts the reading frame of bases

  • changes every codon from point of mutation

• insertion

  • leads to a frameshift mutation

  • shifts the reading frame of bases

  • changes every codon from point of mutation

Effects of mutations

• no effect

  • normally functioning proteins are still synthesised

• damaging

  • phenotype is affected in a negative way as proteins are not synthesised or are non-functional

• beneficial

  • rarely synthesises a protein that results in a new but useful characteristic

Causes of mutations

• can occur spontaneously during DNA replication

• rate of mutation is increased by mutagens (chemical, physical or biological agent which causes mutations)

• depurination - loss of a purine base

• depyrimidination - loss of a pyrimidine base

• free radicals can disrupt base pairing

• antioxidants (e.g. vitamins A, C and E) are anticarcinogens as they negate the effects of free radicals

Mutagens

• physical

  • ionising radiations such as x-rays

    • break DNA strands

• chemical

  • deaminating agents

    • chemically alter bases

• biological

  • alkylating agents

    • methyl / ethyl groups are attached to bases

  • base analogs

    • during replication bind to DNA instead of usual base

  • viruses

    • virus DNA inserts itself into a genome

    • changes base sequence

Chromosome mutations

• deletion

  • section of chromosome breaks off

• duplication

  • sections get duplicated

• translocation

  • section of chromosome breaks off and joins another

• inversion

  • section breaks off, is reversed and rejoins

Transcriptional control

• chromatin remodelling

• histone modiciation

• lac operon

Chromatin remodelling

• DNA is wound around histones - whole complex is a chromatin

• heterochromatin - tightly wound DNA

• euchromatin - loosely wound DNA present during interphase

• if DNA is tightly wound, transcription isn’t possible

• protein synthesis occurs during this time (interphase)

Histone modification

• DNA coils around histones (+ charged whereas DNA is -)

• acetylation or phosphorylation reduces the positive charge on histones

  • causes DNA to coil less tightly

• methylation makes histones more hydrophobic

  • makes them bind more tightly to each other causing DNA to coil more tightly

• epigenetics - control of gene expression by the modification of DNA

Lac operon

• operon - a group of genes under the control of the same regulatory mechanism and are expressed at the same time

• more common in prokaryotes

• glucose is preferred substrate but if it is in short supply, lactose can be used

• structural genes - lacZ, lacY, lacA

• regulatory gene codes for a repressor protein (prevents transcription of structural genes in the absence of lactose)

• binds to the operator (prevents RNA polymerase binding to DNA and beginning transcription)

• promoter - section of the DNA that is the binding site for RNA polymerase

• if lactose is present, it binds to the repressor protein, changing the shape

  • means it can no longer bind to the operator

  • RNA polymerase can bind to the promoter

  • structural genes are transcribed

  • enzymes are synthesised

Role of cyclic AMP

• transport of glucose into a cell decreases the levels of cAMP

• reduces transcription of the genes responsible for metabolism of glucose

Post/Pre-transcriptional control

• RNA processing

  • product of transcription is pre-mRNA which is modified to form mature mRNA

  • cap is added to 5’ end and a tail is added to the 3’ end

  • stabilise mRNA and delay degradation

  • cap aids binding of mRNA to ribosomes

  • splicing - RNA is cut at specific points, introns removed and exons joined together