Module 6 - Genetic Change

Question 1

mutagen

Answer 1

an environmental agent that alters DNA and causes mutations. Many mutagens are carcinogenic (cancer causing) as some mutations occur in genes that regulate the cell cycle, or in genes that promote or supress cell division. This may result in increased cell differentiation = mass of cells (tumours).

Question 2

5 criteria

Answer 2

1. The origin / cause of mutation
   • Spontaneous mutations: arise randomly as a result of an error in a natural process such as DNA replication
   • Induced mutations: caused by a mutagen, an environmental agent (chemical, etc)
2. The amount of DNA changed
   • Point/gene mutation: changes to a single base pair of DNA, affects a single gene
   • Chromosomal mutations (larger): move whole blocks of genes to different parts of a chromosome or to a different one entirely
3. The affect of the mutation on DNA
   • Change in amino acid: base change leads to a triplet code that codes for a different amino acid
   • No change in amino acid: base change leas to a triplet code that codes for the same amino acid
4. The affect of the mutation on phenotype
   • Silent mutation: no change seen in the phenotype
   • Change in phenotype: a small or large change in phenotype depending on the change in DNA and amino acid (harmful or useful)
5. Heritability of mutation
   • Sematic mutation: occurs in a non-reproductive cell. Usually results of environmental factors. The mutation is not passed along to the next generation
   • Germline mutation occurs in reproductive or germline cell. Therefore mutation is passed to offspring.

Question 3

types of mutagens

Answer 3

Chemical, naturally occurring, physical

Question 4

Chemical mutagens

Answer 4

• cause mutations if cells are exposed at high frequencies or long periods of time
• ingested chemicals (alcohol, tar in tobacco smoke, some medications, chemicals in food)
• environmental irritants and poisons (organic solvents like benzene, cleaning products, asbestos, coal tars, pesticides, some hair dyes)

Types

• intercalating agents
• base analogue
• DNA reactive chemicals

Question 5

Chemical mutagens, intercalating agentts

Answer 5

Inserts into bonds between base pairs and alter the shape of DNA, leading to replication errors. A common laboratory stain used to visualise DNA on agarose gels, ethidium bromide, is an example.

Question 6

Chemical mutagens, base analogue

Answer 6

Accidentally incorporated into DNA, replacing normal base pairs as they are structurally similar enough to nitrogen bases, meaning that the DNA no longer functions.

Question 7

Chemical mutagens, DNA reactive chemicals

Answer 7

Chemicals that react directly with DNA (e.g. reactive oxygen species / ROS) which can cause breakages and cross-links in DNA strands.

Question 8

Naturally occuring mutagens

Answer 8

Naturally occurring mutagens
Present at normal levels within natural environments - likelihood of mutations increases with frequency and exposure. These can be divided into
biological mutagens (viruses, bacteria, fungi and products) and
non-biological mutagens (metals such as mercury and cadmium).

Types:
microbes
transposable elements
end products of metabolisms

Question 9

Naturally occurring mutagens, microbes

Answer 9

oncogenic viruses: a gene which can transform a cell into a tumour cell - retroviruses such as HTLV-1 (responsible for types of leukemia and HPV). At least 6 viruses are thought to account for 15-20% of all cancers.
Bacteria: infection with H. pylori increases risk of gastric cancer.

Question 10

naturally occurring mutagens transposable elements

Answer 10

Short sequences of DNA that can move up and down the genome – common in eukaryotic cells. Causes issues when inserting in the middle of a functional gene, creating errors in structure and replication– e.g. the original mutation for haemophilia.

Question 11

naturally occuring mutagens, end products of metabolisms

Answer 11

Plants, fungi or animal cells can produce biological mutagens during cell metabolic activity – example = nitrosamine (chemical present in meat and fish – cooking / processing / smoking causes nitrites and amines to combine, forming the nitrosamine)

Question 12

physical mutagens

Answer 12

Radiatiom – an emission / movement of energy through space or material. Carcinogenic in ionising radiation (high frequency end) which contains enough energy to affect the electric charge of DNA and can break the chemical bonds leading to damage (dependent on dosage and frequency).

Question 13

effect of UV as physical mutagen

Answer 13

UV falls into the category of ionising radiation (skin cancer), most common effect being production of pyrimidine dimers (cross linked nucleotides) – occurring when two base pairs next to each other (either thymine or cytosine) become attached to each other, inhibiting them from pairing correctly and thus preventing normal replication and transcription.

Question 14

Types of Pointmutations

Answer 14

Substitution mutation (missense, non-sense, silent) 
Frame shift mutation (insertion, deletion)

Question 15

Point mutations, substitution mutation, missense

Answer 15

Missense mutation:

• A substitution which leads to the replacement of an amino acid
• The protein is still produced but there is a change in AA and phenotype
• E.g. sickle cell disease (Val replaces Glu), resulting in a distorted shape sickle cell due to altering the haemoglobin protein.

Question 16

point mutation, substitution mutation, non-sense mutation

Answer 16

Non-sense mutation:

• A substitution which leads to the creation of a stop codon (UAA, UAG, UGA)
• If they occur to soon in a gene sequence, the full protein cannot be produced, creating non-functioning proteins.
• Example: thalassemia (blood disorder) – inadequate amounts of haemoglobin. In the gene sequence code (147 codons long), codon 17 is mutated.

Question 17

point mutation, substitutino, silent

Answer 17

Silent Mutation:

• A substitution which leads to a codon which has changed a base but still codes for the same amino acid, therefore no affect on final polypeptide protein.
• E.g. GGG  GGU creates same protein

Question 18

Frameshift mutation - insertion

Answer 18

• A point mutation where one base pair is inserted into sequence so that every codon past the point is shifted forward.
• E.g. Sclerostin – causes people to gain bone mass throughout their lives instead of losing it.

Question 19

Frameshift mutation - deletion

Answer 19

• A point mutation where one base pair is deleted from the DNA sequence so every codon after is shifted back 1. Significant impacts.
• E.g. cyclopia (characterised by the development of 1 eye)

Question 20

Chromosomal / block mutaitons

Answer 20

move whole blocks of genes to different parts of a chromosome or to a different chromosome.

types: deletion, duplication, inversion, translocation

Question 21

Types of chromosomal block mutations

Answer 21

Chromosomal deletion - A large section of DNA is lost (large reduction of genes), often a result of exposure to high heat, viruses or radiation
Chromosomal duplication - A portion of DNA is duplicated and inserted, increasing number of genes.
- The effects depend on the amount and location (exon or intron)
Chromosomal Inversion - Portion of DNA is removed, turned 180O and reinserted. Bases are now in reverse order
- E.g. haemophilia
Chromosomal translocation - Portion of DNA is moved from one chromosome to a non-homologous chromosome

Question 22

aneuploidy

Answer 22

presence of an abnormal number of chromosomes in a cell

Question 23

somatic mutation

Answer 23

• Most mutations occur somatic body cells

- These are not inherited by the descendants of that individual

Question 24

germline cell mutation

Answer 24

• Some mutations occur in germline cells in the gonads (production of gametes)
• These may be inherited by the descendants of that individual or successive generations
• This may increase variation within a population

Question 25

exons

Answer 25

coding segments

Question 26

introns

Answer 26

non coding segments

Question 27

gene expression through RNA processing gene regulation

Answer 27

• Normal transcription occurs (involving both introns and exons)
• RNA processing – splicing (occurs in the nucleus). The spliceosome (enzyme) removes the introns to form pre-mRNA.
• Gene regulation – alternative splicing (occurs in nucleus). The exons are assembled into a mature mRNA (which goes off for translation) and are in slightly different orders each time – increased range of proteins can be produced in complex organisms. This is termed iso-protein (which have similar structure but are not identical)
• Spliceosome binds to the different points along the intron at the sliceosome binding site (snRNP) (5’ junction and 3’ junction – allowing the intro to fold into a loop around the spliceosome complex, and removes the intron from the strand of mRNA)
• Ending up with the exons free of introns

Question 28

deep intronic mutations

Answer 28

Mutations near binding / splice sites

• If a mutation happens near the binding site (inside the intron) – more than 100 nucleotides form the binding site, the section can start looking like a binding site (therefore splicing occurs at the wrong place).
• Deep itronic mutation resembles a binding / splice site = an incorrect splicing by the spliceosome
• Due to incorrect splice site, the spliceosome attaches at the wrong place and not all the intron is removed

Question 29

pseudo exon mutations

Answer 29

Mutations at binding / splice sites (the 5’ junction and 3’ junction)

• If a mutation happens at the binding site, splicing may fail to occur
• Intron non-coding sequence will be read as exon coding sequence with translation occurs (therefore the cut doesn’t occur, altering the structure of the protein)
• Affects: the intron that’s incorrect included may contain sequences that regulate transcription and translation – so can be reduce or increase amount of protein produced

Question 30

gene mutations and promoter regions

Answer 30

• A promoter is a region of DNA that initiates transcription of a particular gene
• In a gene: promoter, coding region, termination sequence
• Terminator region are genetic parts that occur at the end of a gene and cause transcription to stop
• If there are mutations at either end, there will be too much/ too little protein.

Question 31

causes of variation in population

Answer 31

mutation, fertilisation, meiosis

Question 32

Causes of variation: mutations

Answer 32

• Mutations as a source of new alleles – lead to variation (as an allele is a variant form of a gene), can be harmful or helpful

Question 33

Causes of variation: meiosis

Answer 33

• Early Prophase 1: DNA replication occurs and the sister chromatids pair up. The homologous chromosomes also pair up – crossing over / synapsis occurs. The inside chromatids of homologous chromosomes cross over and swap genes, so the chromatids now contain different combinations of genes. They cross over at the chiasmata.
• Metaphase 1: independent assortment
  The pair of homologous chromosomes lines up at the equator, independent of each other. The maternal chromosomes may be on the right / left – creating a different combination of genetic information at the poles of each cell which will split.

Question 34

Fertilisaiton

Answer 34

random fusion of gametes

Question 35

population genetics

Answer 35

the study of how a population changes over time leading to a species evolving

Question 36

Genetic drift

Answer 36

Allele frequencies of a population change over generations due to chance
- The founder effect: happens when a new population is formed from a small number of individual from an existing parent population, but the genetic make up of these ‘founding’ individuals is not representative of the existing population
- The genetic bottleneck: occurs when a population on the brink of extinction grows in numbers again, but the frequency of alleles is hcanged because the few individuals that survived give rise to the new population (which is not representative of the genetic makeup of that original population)
Smaller populations are more vulnerable to genetic drift.

Question 37

Gene flow

Answer 37

• Migration / moving of genes between areas
• If a population is not geographically isolated from other populations, then the movement of individuals from other populations into the population is able to
   Introduce new alleles or
   Change the frequency of alleles in the population
  Gene flow is a result of migration – this deepens the gene pool of the newly migrated island.