Genetic Change and Mutagens

Genetic Change Introduction

• Mutations introduce new alleles into a population
• Mutagens cause mutations that introduce new alleles into a population

Mutagens: Agents of Genetic Change

• Mutagens operate by causing unpredictable and random changes in a cell's genetic material
• Altering the sequence of nucleotides in DNA
• Mutations can arise spontaneously during DNA replication due to uncorrected mistakes
• Environmental factors can also induce mutations

Maintaining DNA Integrity

• Maintaining DNA's integrity is essential for proper cell function
• Mutagens are environmental factors that cause mutations.
• Many mutagens are carcinogenic because mutations can influence cell cycle regulation and cell division, potentially leading to increased cell division without differentiation

Types of Physical Mutagens

• Physical mutations include electromagnetic radiation, heat, and ionizing radiation
• Ionizing radiation involves energy transfer through space
• UV radiation, gamma rays, and X-rays are examples of ionizing radiation
• These high-energy radiations can split electrons from stable nuclei due to their low wavelengths and high energy

UV Radiation Effects

• UVB (280-315 nm) and UVC (100-280 nm) radiation are particularly dangerous
• Natural UV radiation exposure can increase the risk of skin cancer
• UV radiation often causes pyrimidine dimers (cross-linked nucleotides) in DNA

Formation of Pyrimidine Dimers

• Pyrimidine dimers occur when adjacent pairs of bases, typically two thymines or two cytosines, on the same strand attach
• This attachment prevents pairing on the complementary strand and prematurely ends the strand
• Leading to incorrect transcription, translation, and faulty protein production

Effects Of Alpha, Beta, and Gamma Rays

• Alpha, beta, and gamma rays release electrons from stable atoms
• These high-energy electrons create free radicals by interacting with water and biomolecules within cells
• Free radicals are highly reactive and can alter the protein and lipid structures of the body
• Resulting in deletions, partial chromosome loss, or rearrangements of sequences from cross-linked DNA

Chemical Mutagens

• Chemical mutagens cause mutations when cells are exposed at high frequencies or for prolonged durations
• Many ingested and everyday chemicals have been identified as mutagenic
• Chemical mutagens can alter the function of proteins and cellular processes by changing DNA

Examples of Chemical Mutagens

• Ingested chemicals like alcohol, tar in tobacco, smoke, medications, and food additives
• Environmental irritants such as organic solvents, cleaning products, asbestos, coal tars, pesticides, and hair dyes
• Alkylating agents, like chemotherapy drugs, add alkyl groups to guanine, leading to DNA strand breakage during replication
• Deaminating agents remove amino groups from bases, which can cause uracil to form from cytosine, leading to mutations
• Intercalating agents insert themselves between DNA bases, deforming the helical structure and causing frameshift mutations
• Actinomycin D is an example used in chemotherapy to kill cancer cell DNA

Naturally Occurring Mutagens

• A biological process are end products of metabolism from fungi, plants, or animal cells during metabolism
• Some toxic metabolites act as alkylating agents
• Metabolizing methanol produces formaldehyde, which alkalizes purine bases
• Transposons are sections of DNA that spontaneously fragment, relocate, multiply, and insert themselves into DNA, altering its function
• Microbes, such as viruses and bacteria, are naturally occurring biological mutagens that can alter genetic material
• Heavy metals like mercury and cadmium are also naturally occurring non-biological mutagens that can alter DNA

DNA Repair Mechanisms

• Cells have multiple repair mechanisms to correct different types of DNA damage

Base Excision Repair

• Repairs spontaneous damage to DNA bases, involves DNA glycosylase
• Glycosylase recognizes and removes the damaged base, flips and snips the DNA
• An AP site forms, and AP exonuclease inserts the correct base
• DNA polymerase I refills the next couple of bases and connects the DNA backbone using ligase

Mismatch Repair

• Used when an incorrect base is mismatched and does not bond
• System of enzymes finds and removes the faulty strand
• Econuclease excises a section of DNA, resynthesized by DNA polymerase, ligase reconnects the backbone.

Nucleotide Excision Repair

• Repairs damage from chemicals and radiation causing pyrimidine dimers
• Excinuclease finds the damage and removes a 12-nucleotide strand
• DNA polymerase replaces the missing bases, and ligase rejoins the strands

Point vs Chromosomal Mutation

• Mutations are any change in DNA, different types can be distinguished by different criteria

Criteria for Distinguishing Mutations

• Origin: Spontaneous or induced
• Amount Changed: Point, gene, or frameshift mutation
• Effect on DNA: Substitution, insertion, or deletion
• Effect on Phenotype: Silent, variation, harmful, or beneficial
• Heritability: Somatic or germline mutation

Point Mutations

• Point mutations are single nucleotide variations that can significantly impact phenotype if in an exon or intron
• Most result in base substitutions, but some create a frameshift
• Can lead to new amino acids being inserted into the polypeptide chain, demonstrated in sickle cell anaemia

Frameshift Mutations

• A point mutation involving the insertion or deletion of a single nucleotide pair
• Alters how mRNA reads DNA and can result in a completely non-functioning protein

Types of Mutations

• Nonsense mutation: Changes an amino acid to a stop codon, resulting in a shortened, non-functioning
• Missense mutation: Point mutations leading to an amino acid change, function is determined by the replaced amino acid
• Silent mutation: Changes in the DNA sequence that do not alter the amino acid, having no effect on proteins
• Neutral Mutation: Changes in DNA resulting in an amino acid of the same type as the original

Chromosomal Mutations

• Mutations on a larger scale alter the structure or number of chromosomes
• Also known as chromosomal aberrations, they may involve changes to a series of bases
• Gene mutations are any changes to the DNA sequence within one gene

Chromosomal Rearrangement/Structure Mutations

• Chromosomal deletion: A section of DNA is removed and not replaced, leading to fewer
• Chromosomal insertion: A portion of DNA is duplicated/doubled and inserted, increasing gene number
• Chromosomal inversion: A section of DNA is removed, turned back to front, and reinserted, reversing the gene order
• Chromosomal translocation: A section of DNA is moved from one chromosome to a nonhomologous chromosome, which may lead to gene fusion

Chromosomal Number Alterations

• Nondisjunction: Homologous chromosome pairs do not segregate correctly during anaphase in meiosis I or II
• Aneuploidy: One or more extra copies of an entire chromosome are made, or one is entirely missing

Somatic vs. Germline Mutations

• Mutation effects are on a cellular, individual, and population level
• Cellular considers the type of cell affected, with germline mutations being heritable
• Individual effect is the phenotypic expression
• Population introduces new alleles with possible beneficial or harmful variation
• Heritable mutations can be passed on (germline), potentially affecting phenotype & natural selection

Somatic Mutations

• Occur in somatic cells, often due to replication errors before mitosis
• Spontaneous mutations may occur in the S phase of the cell cycle
• If not repaired, they will be passed onto daughter cells in mitosis
• Continued divisions multiply the error, amplifying issues and leading to phenotypic differences, such as cancer
• Somatic mutations can be unobservable: physiological changes, such as cystic fibrosis

Germline Mutations

• Gametic mutations occur in gametes and are passed onto offspring
• When a gamete carrying the mutation fuses with another, the mutation is replicated in every cell, from the developing embryo onwards
• Tay-Sachs disease is an example of a disease caused by a germline mutation

Coding vs. Non-Coding DNA

• Mutations in coding genes usually affect the type or sequence of amino acids in the resulting polypeptide
• Exons are responsible for building proteins and phenotypic expression
• These mutations in introns can influence sequence of codons
• Exons are integral, thus mutations affect synthesis
• Most DNA in prokaryotes is coding
• Maintaining DNA integrity is essential for microbial survival due to continuous exposure to changing environments
• Errors in eukaryotic genes for DNA repair are serious and increase mutations from replication errors
• Mutations in tumor suppressor genes or proto-oncogenes can result in cancer

Non-Coding Segments of DNA

• Telomeres: Mutations that shorten telomeres and can interfere with continuous cell replication
• Introns: Mutations can lead to a frameshift mutation
• Centromeres: Alteration/compromisation leads to negative effects in chromosomal division
• Promoters: No protein can be made if the promoter is affected by a mutation
• Other segments are responsible for the production of telomeres, satellite DNA, centromeres, heterochromatin structural segments
• Genetic variation is tied to fertilization, meiosis, and mutation

Genetic Variability:

• Recombination during gamete formation and fertilization increase genetic recombination
• An increased number of alleles for a particular gene further increases variability
• Mutation increases the number of alleles for a trait
• The 3 processes that induce genetic variation
  • Mutation produces new alleles and changes in gene regulation, expression, chromosomal number, and arrangement
  • Meiosis provides variation through crossing over, independent assortment, and random segregation, resulting in new combinations of chromosomes and alleles
  • Fertilisation allows new combinations of alleles

Genetic Drift

• Change in allelic frequency in a population due to random events, natural disaster etc
• Allelic frequency of the surviving population will increase, by means of reproducing, or exiting a population

Gene Flow

• The process of alleles moving from one population to another, by organisms leaving or entering the population.

Gene Pool

• The allele total is altered as a result of natural selectionrandomly In either case the allele total (gene pool) is altered as a result of natural selection, or randomly by genetic drift or gene flow

Darwins findings

• Natural selection is the primary driving force for evolution
• If a gene confers an advantage, it is more likely to be passed onto the next generation

Changes to Allele Frequency

There are five causes of allele frequency within a population:

• Selective pressure causes changes in allele frequency based on variations that allow species to live on
• Sexual selection is when the most successful mates of the given species are able to pass on the allele traits
• Mutation leads to the development of new allele
• Genetic drift changes allele frequency via random chance.
• Gene flow changes allele frequency in a population by mixing of new individuals with old ones

Biotechnology Uses and Applications

• Encompasses commercial exploitation of biological processes, particularly in research and development based on new biological discoveries

Past Biotechnology

• Ancient Agriculture: Domestication of plants and animals began approximately 10,000 years ago then were selectively bred
• Using microorganisms for bread - Yeast in bread, and bacteria in cheese
• Fermentation was discovered roughly 6,000 years ago used to produce alcohol

Present Biotechnology

• DNA Splicing: Cutting out genes using restriction enzymes to break up foreign DNA
• DNA Amplifying: Copying genes through PCR, allowing replicated gene insertion
• Recombining DNA: Pasting genes with DNA ligase to form recombinant DNA/transgenic species
• Agarose Gel Electrophoresis: Analyses DNA and identifies DNA fingerprints
• Gene Probes: Using specific lengths of single-stranded DNA complementary to known DNA. Can detect the DNA by manufacturing artificially tagged w fluorescent dyes
• DNA Profiling: PCR amplification of short tandem repeats (STRs) followed by gel electrophoresis.
• Includes selective breeding, artificial pollination, artificial insemination, transgenesis, genetic cloning, and DNA hybridization

Industrial Biotechnology

• Pollution Prevention: Bioleaching, Biopesticides, Biofuels, enzyme that degrades pesticides
• Biomaterial Production: Bioprinting, GM yeast (converts waste)

Medical Biotechnology

• Reproductive Technology: Contraceptives, IVF
• Antibiotics: Vaccines and Drugs (Penicillin, anti-Smallpox, Aspirin)
• Human proteins, includes; Insulin, HGH, Factor ix
• Tissue and organs cultural bioprinting for gene therapy

Agricultural Biotechnology

• Waste management: microbes and enzymes
• Artificial insemination w cloned pollination
• Selective breeding: herbicide species

Ethical Implications of Biotechnology (Individual Morals)

• Bioethics: ethical issues concerning sovereignty over life (Creation and religion)
• Endangers human life (IVF, embryo screening)
• Participation harm (harmful treatments/mutations)
• Immoral treatment of animals
• Objectionable genetic materials

Social Implications of Biotechnology (Population/Society)

• Less risk from disease and genetic disorders
• Lowered harmful alleles
• Economic imbalance (status/accessibility)- developed markets dominant
• Removing natural selection- leading to no variability
• Unequal for people

Specific Examples in Biotechnology and Animals

• Allowed for selective breeding/GM to modify produce of dairy or milk
• Religions object (beliefs)
• Concerns of animals infecting humans, harm and moral

Specific Examples in Plants (GM Soybeans)

• Ethical concerns for farmer success
• Allergens created
• Vegetarian plants contain animal allergens

Future Biotechnology Directions

• Biotechnology is exponentially growing beginning biotech revolution
• Growth larger than computer advancement
• Could cure and prevent diseases
• CRISPRS; cuts and splices genes
• Removes neurological diseases, or used for ""designer babies""

Potential Societal Benefits of Biotechnology

• Synthetic meat ends hunger for benefit of climate- impacts farmers
• Life extension benefits by reducing suffering via Insurance but may cause overpopulation

Changes to Earths Biodiviersity

• Modern biotechnology removes the randomness, increasing the amount of traits available
• Can build a monoculture, where every organism has favored alleles; could eliminate horizontal gene transferring

Selective Breeding

• Traits passed to generations artificially

Artificial Insemination

1. Gathering semen
2. Dividing that semen
3. Thawing semen
4. Depositing it to the needed animals

Aritificial Pollination

• Brush selected pollen onto each stigma New breeds form

In Vitro Fertalization

• Infertility can breed with select gammets. May cause monoculture

Gene Cloning

• At the cellular level, used for big amount production of gene
• Remove gene from organism and inset elsewhere, commonly for mass scale productions

Steps of Gene Cloning

1. Restric the gene and ezyme
2. Paste vector with DNA
3. Tranfsfer the cell
4. Let repliaction start

Polymerase Chain Reaction

• A form of cloning to produce the aount of DNA Process

1. Denaturation ( separate the DNA)
2. Ennealing ( match primers and specific DNA)
3. Elongation (add DNA with polymere). Process
4. Use of cell
5. Remove nucleus/enucleate
6. Fusing of cells
7. Placed where birth can occur

Cloning Assestment

Scottish Blackface (Cytoplasmic Donor) Finn-Dorset (Nuclear Donor)Enucleation