DNA Structure, Genes and Replication

• DNA coils around proteins called histones.
• When a cell is not dividing, DNA forms a tangled network called chromatin.

Genes

• Genes are sections of DNA that code for the production of a protein.
• Genes can be switched on or off, which determines the production of proteins.

Chromosomes

• Chromosomes are long lengths of DNA with many genes.
• Humans have 46 chromosomes, which is 23 pairs.

Structure of DNA

• Nucleotide: the basic unit of a DNA molecule.
• Each nucleotide has a phosphate group, a deoxyribose sugar, and one of four different nucleotide bases.
• Four possibilities for the base: Adenine (A), Thymine (T), Guanine (G), Cytosine (C).
• The bond between the bases is a weak hydrogen base.

Replication of DNA

• DNA is a molecule able to produce exact copies of itself.
• It replicates during interphase, ensuring each new daughter cell gets a complete copy of the genetic instructions.
• The molecule separates via the weak hydrogen bonds between the bases.
• The two halves serve as templates for the nucleotides that form the new half.
• Base pairing rules ensure the new half is identical to the original.
• DNA can only be synthesized in the 5' to 3' direction.
• One strand is synthesized continuously while the other occurs in discontinuous sections known as Okazaki fragments.

Enzymes in DNA Replication

• Helicase: unwinds the parental double helix.
• Binding proteins: stabilize separate strands.
• Primase: adds short primer to the template strand.
• DNA polymerase: binds nucleotides to form new strands.
• DNA polymerase I (exonuclease): removes the RNA primer and inserts the correct bases.
• Ligase: joins Okazaki fragments and seals other nicks in the sugar-phosphate backbone.

Role of DNA in the Cell

• DNA codes for the production of proteins; the formation of these proteins is known as protein synthesis.
• Proteins are formed by linking a chain of amino acids.

Protein Synthesis

• Synthesis combines small molecules to make larger ones.
• Protein synthesis is combining small amino acids to form large protein molecules.
• Genes contain DNA that code for a particular protein.
• Protein synthesis occurs in two stages: transcription and translation.

Transcription

• Amino acids are joined together at the ribosome in the cytoplasm.
• DNA molecules are too large to leave the nucleus.
• The process of making an mRNA molecule from DNA is transcription.
• Helicase causes the two strands of the DNA in a gene to separate.
• RNA polymerase begins to make mRNA by joining nucleotides with bases complementary to those on the DNA template strand.
• The newly formed mRNA moves through the nuclear pore into the cytoplasm when that section of DNA is copied.

Translation

• mRNA attaches to the ribosome at a point on the mRNA known as the binding site.
• The ribosome reads along the mRNA until it reaches an A-U-G sequence.
  • This indicates the start of a protein; it is the code for the amino acid, Methionine.
  • All proteins will start with Methionine.
• The ribosome reads each group of three bases from this point; each group is called a codon.
• Each codon codes for a particular amino acid.
• Transfer RNA (tRNA) carries the amino acids to the ribosome.
• The tRNA will display a codon opposite to the one on the mRNA (anti-codon).
• Three bases of the anticodon (tRNA) carrying the amino acid bind with the three bases of the codon (mRNA).
• Amino acids are bonded together (in the correct sequence) to form a peptide chain.
• tRNA molecules detach from the amino acid, then return to collect another amino acid in the cytosol.
• The chain of amino acids then goes through a folding process, so the final shape of the protein is vital to its function.

Cell Division

• Binary fission is a form of asexual reproduction in prokaryotic cells.
• A single chromosome is tightly coiled before binary fission.
• DNA replication occurs in the chromosome and any plasmids.
• The two copies attach to the cell membrane and are pulled to opposite ends.
• A cleavage furrow develops, and a new cell wall also develops.
• The new cell wall divides the cell completely.
• The two cells separate, and are both genetically identical to the parent cell.

Mitosis and the Cell Cycle

• Organisms must increase their number of cells to grow in size.
• Organisms do this by cell division using the cell cycle.
• Cells move through a series of phases in the cycle.
• Cells are in interphase for most of the time; molecules are synthesized, and DNA is replicated at this stage.
• Cell division occurs in two stages: division of the nucleus containing the chromosomes (mitosis) and division of cytoplasm (cytokinesis).

G1 Phase

• The G1, or first growth phase, is the period in the cell cycle during interphase before the S phase.
• This is the major period of cell growth during its lifespan for many cells.
• A cell may pause in the G1 phase before entering the S phase and enter a dormant state called the G0 phase.

S Phase

• The S phase is the part of the cell cycle where DNA is replicated.
• It occurs between the G1 and G2 phases.
• Precise and accurate DNA replication is necessary to prevent genetic abnormalities that can lead to cell disease or death.

G2 Phase

• The G2, or second growth phase, is the third and final subphase of interphase.
• It directly precedes mitosis.
• A period of rapid cell growth and protein synthesis in which the cell readies itself for mitosis.

Interphase

• Chromosomes are not visible, they are non-condensed chromatin.
• Growth and DNA replication occur.

Mitosis - Prophase

• Chromosomes condense and become visible.
• Each chromosome is double-stranded.
• The two copies, called chromatids, are held together by a constricted region called the centromere.
• The nuclear membrane begins to break down.
• Spindle fibers form at the poles of the cell.

Mitosis - Metaphase

• Chromosomes line up along the equator of the cell.
• Centromeres attach to spindle fibers.

Mitosis - Anaphase

• Spindle fibers contract.
• The centromere is pulled in the opposite direction and splits.
• Chromatids separate and move to opposite poles.

Mitosis - Telophase

• Chromatids reach the poles of the cell.
• The nuclear membrane reforms around each group of chromosomes.
• Chromosomes un-condense.

Cytokinesis

• Cytoplasm divides to produce two new ‘daughter' cells.

Meiosis

• Meiosis is the process of cell division that produces gametes.
• Daughter cells only have half of the DNA of the parent cell; they are not exact DNA copies of the parent cell.
• Two cell divisions are involved.
  • Meiosis I: homologous chromosome pairs separate.
  • Meiosis II: sister chromatids separate.
• Four gametes are produced.

Meiosis I – Prophase I

• Chromosomes condense and pair with their homologous partner.
• Crossing over occurs.
• Homologous chromosomes exchange different segments of their genetic material to form non-identical chromatids (resulting in a new combination of alleles).

Meiosis I – Metaphase I

• Homologous pairs line up in the middle of the cell.
• Differs from metaphase in mitosis, homologous pairs are lining up in the middle, not individual chromosomes.

Meiosis I – Anaphase I

• Homologous pairs are pulled apart and move to opposite ends of the cell.

Meiosis I – Telophase I

• Chromosomes move to opposite ends of the cell.
• The nuclear membrane reforms with one chromosome in each.
• Chromosomes de-condense.

Meiosis II

• Each of the two cells produced in meiosis I divides again.

Meiosis II - Prophase II

• Chromosomes re-condense.
• The nuclear membrane breaks down again.
• Centrosomes move apart, and spindles form.

Meiosis II - Metaphase II

• Chromosomes line up in the middle.

Meiosis II - Anaphase II

• Sister chromatids separate and are pulled toward opposite ends of the cell.

Meiosis II - Telophase

• Nuclear membranes form around each set of chromosomes, and chromosomes decondense.

Variation and Mutation

• Variation: the differences between members of a species.
• Three main mechanisms influence variation in a population: environmental factors, mutation, and reproductive processes.

Environmental Factors

• The phenotypic expression of genes depends on the interaction of genes and the environment.
• These factors can be internal, like gender.
• These factors can also be external, like temperature.
• They can also be epigenetic, like stress.
• Genes can be enhanced (acetylation) or inhibited (methylation) from transcription; this will influence the phenotype of the organism.

Mutations

• Mutations are permanent changes to an organism's DNA.
• Spontaneous mutations occur during DNA replication or cell division.
• Mutagens: physical, chemical, or biological factors in the environment that can induce mutations (e.g., UV radiation, mustard gas, and bacteria).
• If a mutation occurs in a somatic (body) cell, it only affects that cell and any daughter cells produced through mitosis.
• If a mutation occurs in a germline (sex cells), they can be passed on to the next generation during fertilization; these mutations will affect every cell of the offspring.

Causes of Mutations

• Errors in DNA replication and cell division.
• DNA replication errors.
• Incorrect base pairing can occur during DNA replication, spontaneously or caused by a mutagenic agent.
• Cell division errors.
• Mutation can occur during mitosis or meiosis when the separation of chromatids or homologous chromosomes is unequal.
• Mutation can occur during crossing over in meiosis when sister chromatids misalign; one may gain extra nucleotides (insertion mutation) or lose nucleotides (deletion mutation).

Physical Mutagens

• Cause physical changes to the DNA code; nitrogenous bases may be lost or fused, resulting in incorrect base pairing during DNA replication.
• Examples: UV light, X-rays, and Nuclear radiation.

Chemical Mutagens

• Cause chemical changes to the DNA code; nitrogenous bases can be substituted with an incorrect base or a foreign molecule, which may result in incorrect base pairing during DNA replication.
• Examples: mustard gas, colchicine, and 5-bromouracil.

Biological Agents

• Mutations can occur due to invasive pathogens such as viruses and bacteria.
• DNA from the pathogens can become permanently integrated into the host cell to be passed on to daughter cells.

Types of Mutations

• Point mutations: when a single nucleotide is affected by substitution, addition, or deletion.
• Substitution: when one nucleotide is replaced by another, also known as a single nucleotide polymorphism (SNP's “Snips").
  • If a SNP occurs within a protein coding gene, the mutation can have several possible effects.
• Insertions and deletions: When one or more nucleotides are gained (insertion) or lost (deletion) from within the original gene sequence; this usually results in a frameshift mutation.

Chromosome Mutations

• Involve missing or duplicated whole or large sections of chromosomes.
• Identification of chromosome differences can be displayed and analyzed by producing a karyotype of the organisms' chromosomes.

Variations in Chromosome Number

• Most eukaryotic organisms have somatic cells that are diploid (2n).
  • The cells contain two sets of chromosomes, one from each parent.
• This is not always the case and can be normal for some species; variations in chromosome number can also occur because of mutation.
• Monoploidy: when an organism has haploid somatic cells (e.g., some colonial insects have monoploid males and diploid females).
• Polyploidy: the failure of chromosome separation during meiosis can sometimes result in diploid gametes.
  • When fertilization occurs, diploid x haploid = triploid (3n) and diploid x diploid = tetraploid (4n).
  • Polyploidy is common in plants and algae.
• Aneuploidy: the addition or loss of one (or a few) chromosomes from a cell.
  • This can happen during mitosis (e.g., Tasmanian devil tumor cells) or in meiosis during the production of gametes.
• Nondisjunction: During Meiosis, when the pairs line up and then separate, one or more of the chromatids may fail to separate.
• Trisomy: results from an extra chromosome. "Tri" meaning three (of a particular chromosome)
• Monosomy: results when a chromosome is missing. "Mono" single chromosome
• During Meiosis when the pairs line up and then separate, one or more of the chromatids may fail to separate; this is known as non-disjunction.
  • Results in one of the daughter cells receiving an extra chromosome and the other daughter cell lacking that chromosome.
  • Nondisjunction can happen in Meiosis I or Meiosis II.
• Trisomy: results from an extra chromosome ("Tri" meaning three).
  • Example: Trisomy 21 (Down syndrome).
• Monosomy: results when a chromosome is missing ("Mono" single chromosome).
  • Example: Turner's syndrome.

Variations in Chromosome Structure

• Deletions: when a section of a chromosome is missing.
• Inversions: when a section of chromosome breaks off, inverts and rejoins.
• Translocations: when a section of a chromosome breaks away from one chromosome and attaches to another.
• Duplications: when an extra copy of a section of a chromosome is attached to the same or another chromosome.
• Sexual reproduction increases variation.
• Crossing over: when homologous pairs of chromosomes swap alleles during prophase I of meiosis.
• Independent assortment and random segregation: maternal and paternal chromosomes are oriented randomly on the equator during metaphase 1; each is independently assorted left or right to the poles before the first division.
• Random fertilization: it is impossible to determine exactly which sperm will fertilize which egg.
  • Fertilization is random and results in a unique individual being produced each time the process is carried out.