Mutations and Mutagens

Mutations

• Mutations are permanent alterations in the DNA base sequence
• They can arise spontaneously due to replication errors or be induced by external factors
• Mutations may be harmful (causing diseases), neutral (affecting non-coding DNA), or beneficial
• Mutations introduce new alleles into populations and generate genetic variation

Mutagens and Mutagenesis

• Mutagens are environmental agents inducing mutations; the introduction of a mutagen is mutagenesis

Electromagnetic Radiation as a Mutagen

• Electromagnetic radiation includes visible light, gamma rays, and X-rays
• Radiation transfers energy, including heat and ionizing radiation
• Ionizing radiation breaks chemical bonds in DNA, creating free radicals
• UV radiation from sunlight can damage the cell cycle by causing adjacent base pairs to connect, hindering their ability to pair with complementary bases

Chemical Mutagens

• Mutagenic chemicals are similar to DNA bases and are incorporated into DNA, resulting in mispairing of nucleotides
• Sources include alcohol, cigarette tar, asbestos, pesticides, and cleaning products

Naturally Occurring Mutagens

• The chance of mutation increases with frequency and exposure to naturally occurring mutagens
• Biological mutagens such as microbes (viruses, bacteria, fungi like Hepatitis B and HPV) can cause mispairing
• Other sources include metabolism end-products and transposons, which disrupt DNA function and can trigger cancers
• Non-biological mutagens include mercury and cadmium

Point Mutations

• Point mutations involve changes to the sequence of a single base during transcription, potentially altering the amino acid sequence and protein
• Substitution: One base is replaced with another, with varying effects
• Insertion/Deletion: A base is added or deleted, leading to frameshift mutations that cause a major change in the amino acid sequence
• Inversion: Two bases are swapped
• Silent: Does not alter the amino acid sequence, resulting in no effect (e.g., different codons code for the same amino acid)
• Nonsense: Creates a premature stop codon, ending the sequence and having a serious effect
• Missense: Alters one amino acid, with varying effects such as in sickle cell anemia
• Neutral: A type of Missense mutation that results in an amino acid of the same type as the original, causing no significant effect

Chromosomal Mutations

• Chromosomal mutations involve changes to a series of bases
• Chromosome Structure:
  • Duplication: Part of the chromosome is copied, duplicating segments and genes, with effects depending on the size and location -Inversion: A segment is removed, flipped, and replaced
  • Translocation: Segments of two chromosomes are exchanged
  • Deletion: A segment and its genes are lost

Chromosome Number (Aneuploidy)

• Aneuploidy is an abnormal number of chromosomes caused by non-disjunction during meiosis
  • Trisomy: An extra chromosome is present
  • Deletion: A chromosome is missing
  • Polyploidy: There is genome duplication with extra complete sets of chromosomes; fatal in humans and most animals but makes plants more robust

Types of Mutations

• Mutations can be somatic or germline
  • Somatic: Occurring in somatic (body) cells
  • Germline: Occurring in reproductive (germline) cells
• Mutations can be spontaneous or induced
  • Spontaneous: Random, resulting from natural processes
  • Induced: Caused by an environmental agent
• Mutations can be harmful, neutral, or (rarely) beneficial

Somatic vs. Germ-Line Mutations

• Somatic mutations typically result from environmental factors or replication errors, occur in diploid body cells, and cannot be inherited, affecting only individuals
• Somatic mutations usually have no effect unless the mutated cell divides by mitosis, passing the mutation to other cells and amplifying the error; can lead to cancer if a tumor suppression gene is affected
• Germ-line mutations occur in sexual reproductive cells (haploid gametes) and can be passed to offspring, having harmful, neutral, or beneficial effects
• If a mutated gamete fuses with another gamete, the mutation is replicated in every cell of the resulting zygote, significantly affecting the child
• The inheritance of mutations contributes to the gene pool and influences entire populations

Significance of Coding and Non-Coding DNA in Mutation

• Coding DNA (exons) directly codes for proteins (and thus genes), comprising less than 2% of human DNA; mutations directly affect protein production
• Non-coding DNA (introns) contains regulatory genes controlling gene expression, produces tRNA, mitochondrial RNA, and other RNAs involved in gene repair, structure, and regulation; mutations are linked to birth defects, abnormalities, and disease predisposition
• Junk DNA neither codes for proteins nor has regulatory functions

Genetic Variation

• Fertilization can maintain or change gene frequency based on the combinations of genes passed to offspring
• Meiosis: Crossing over in prophase I causes homologous chromosomes to exchange genetic material, producing four genetically different chromatids
• Recombination and unique gene combinations increase genetic variation and create different allele combinations; non-disjunction can also cause chromosomal mutations and alter the gene pool
• Mutation can change gene frequency in a population by altering, creating, or deleting genes, thereby changing the proteins produced

Effects on Gene Pool

• Mutation introduces new genes into the gene pool through replication errors; most are removed unless neutral or beneficial
• Gene flow changes the gene pool as individuals leave (emigrate) or enter (immigrate) a population, more noticeable in small populations, stabilizing the gene pool
• Genetic drift is a change due to chance events (e.g., natural disaster) that leads to individuals being killed or isolated, decreasing genetic diversity
• Sexual selection occurs when certain individuals are more attractive and breed more, increasing the frequency of alleles in those with mating success
• Selective pressure occurs when certain alleles/genes increase the chance of surviving environmental pressures, increasing in frequency as individuals with these genes survive to pass them on

Population Dynamics

• Population bottleneck: Genetic drift occurs when natural/man-made events reduce a population by over 50%, decreasing genetic variation, the gene pool no longer resembles the original
• Founder effect: A small group breaks away from a population and colonizes a new area, resulting in lower genetic diversity and vulnerability; as the population increases, it no longer resembles the original gene pool

Biotechnology Applications

• Past applications: food production (bread, cheese, wine), medicine, domestication, selective breeding, and antibiotics
• Present applications: DNA manipulation (splicing, amplification, recombinant DNA technology), DNA analysis/visualization (gel electrophoresis, DNA sequencing and profiling), and biofuels
• Gel electrophoresis: DNA fragments are separated by size using an electric current on a gel, then stained to highlight the fragments
• Future applications: (see 'Future directions')

Social and Ethical Implications

• Ethical considerations: non-harm, ethical decisions, individual rights, autonomy, equity, justice, and privacy
• Dolly the Sheep Cloning: Cloned via SCNT, raised questions about human cloning and the health of cloned animals, Dolly lived half the expected lifespan
• Bt Cotton: Uses Bt bacterium toxin gene for pest immunity, reducing biodiversity and increasing vulnerability to environmental change/pests, leading to social and economic problems

Future Biotechnology

• Future directions: more widespread use of cloning and recombinant DNA technology, such as gene therapy
• Potential benefits: gene therapy for treating human diseases, genetically modified foods for alleviating hunger, plant banks and animal cryopreservation for conserving biodiversity, and plant/algae-based resources for biofuels

Biodiversity and Genetic Techniques

• Short-term: New gene combinations lead to increased biodiversity
• Long-term: Selective breeding of certain genes can lead to decreased biodiversity

Genetic Technologies

• Artificial selection (AI and AP): Used to create organisms with desired characteristics, simplifies fertilization and transfers desired characteristics consistently
• Whole-organism cloning: Involves transferring the nucleus of a body cell into an enucleated egg cell and developing it in a surrogate mother, allowing copying of desired characteristics efficiently, useful for conservation
• Recombinant DNA technology: Transfers genes between organisms, moving/deleting/modifying genes; increases genetic diversity, produces organisms quickly, and develops medicine

Gene Cloning

• Involves cutting a desired gene from a chromosome and a plasmid from a bacterium using a restriction enzyme
• A sector is removed from the plasmid, replaced by the gene, and the plasmid is reinserted into the bacterium to multiply
• Used in medical applications like insulin production

Transgenic Organisms

• Involves inserting genes from other species into an organism, exemplified by Bt cotton, allowing advantageous traits to be transferred

Reproductive Technologies

• Artificial insemination involves inseminating a female with male semen from the same species, producing offspring with desired characteristics and reducing genetic variation
• Artificial pollination involves dusting pollen with desired genes onto the stigma of a plant, producing offspring with desired characteristics, can create hybrids leading to short-term genetic variation, but long-term leads to decreased variation

Cloning Effectiveness

• Whole organism cloning produces organisms with identical genotypes to the original using SCNT
• Gene cloning produces copies of a single gene using recombinant DNA technology

Recombinant DNA Technology

• Agricultural: Bt cotton created via recombinant DNA technology inserts toxin gene from bacterium Bt into cotton for pest resistance -decreases pesticide use, increases safety, soil quality, and yields however also decreases biodiversity and increases environmental change and resistance
• Medical: Transgenic mice receive human genes to replicate human conditions and test drugs/medicines, insulin cloning is done through recombinant DNA technology

Benefits of Genetic Engineering

• Agricultural: DNA marker tests breed naturally hornless beef cattle (preventing injury), Bt cotton decreases pesticide use and increases yield/profit, and Al/AP/cloning passes on desired characteristics
• Medical: Transgenic organisms (transgenic mice as disease models, cloning of insulin) increases volumes at low cost; vaccines (cloning antigens of weak and dead pathogenic cells) increase hormones/proteins made, and allows gene therapy
• Industrial: Biofuel improvements through altering bacteria and fermentation, pollution cleaning via genetically modified bacteria for crude oil clean up, produces renewable resources, and is biodegradable

Biotechnology in Agriculture

• Biotechnology in agriculture creates genetically similar offspring, decreasing genetic variation and gene pool
• Widespread use decreases biodiversity and increases extinction risks from environmental changes (disease, pests)

Context of Biotechnology

• Cultural context: values and beliefs influence opinions and uses of biotech
• Social context: society's needs define biotech uses
• Economic context: high GMO costs may cause unequal wealth/opportunity distribution