DNA Structure & Chromosomes Notes

DNA Structure & Chromosomes

Objectives

• Define and use correctly: genotype, phenotype, homozygous, heterozygous, alleles, and genes.
• Discuss the Mendelian model of inheritance.
• Describe patterns of inheritance (e.g., sex linkage, dominant, recessive, codominant, and incomplete dominant).
• Describe genotypic and phenotypic variation.
• Discuss chromosomal variations in humans.

Introduction

• DNA is one of the 4 groups of biomolecules.
  • Monomers are nucleotides.
  • Polymers are called polynucleotides.
• Major nucleic acids:
  • DNA (deoxyribonucleic acid):
    • Stores genetic information in all cells.
    • Very large—about 10 billion atoms.
    • Inherit half of our DNA from each parent.
  • RNA (ribonucleic acid):
    • Necessary for converting DNA’s information into proteins.
    • Several types of RNA.

Nucleotides: Monomers of Nucleic Acids

• Nucleotides are made of 3 parts:
  • A 5-carbon monosaccharide:
    • Ribose in RNA.
    • Deoxyribose in DNA.
    • Shaped as “hut with 1 chimney”.
  • A phosphate group:
    • The functional group $-OPO_3$.
  • A nitrogenous base:
    • A ring structure containing carbon and at least 2 nitrogen atoms.
    • May be a double ring or single ring.

Names of Nitrogenous Bases

• Bases with 1 ring are known as Pyrimidines:
  • Thymine (T).
  • Cytosine (C).
  • Uracil (U).
• Bases with 2 rings are known as Purines:
  • Adenine (A).
  • Guanine (G).
• A, G, C, and T are found in DNA.
• A, G, C, and U are found in RNA.

Sugars on DNA and RNA

• The "D" in DNA stands for "deoxyribo".
  • Ribose sugar minus an oxygen on the lower right of the molecule on the #2 carbon.
• The "R" in RNA stands for "ribo".
  • Ribose sugar with its oxygen.

Differences between Deoxyribose and Ribose

• Deoxyribose lacks an oxygen atom on the 2' carbon, while ribose has an oxygen atom on the 2' carbon.

Nucleic Acids Are Polymers of Nucleotides

• Nucleic acids are polymers of nucleotides that form strands.
  • DNA is 2 strands of nucleic acids wrapped around each other in a double helix.
  • RNA is a single-stranded nucleic acid.
• Nucleotides form nucleic acids by the dehydration reaction.
  • Removing water forms a covalent bond between the phosphate of 1 nucleotide and the sugar of the second nucleotide.
• Single-stranded nucleic acids—RNA:
  • Backbone is made of alternating sugar and phosphate.
  • Held together with a covalent bond.
  • Bases attached to sugar with covalent bonds.
• Double-stranded nucleic acids—DNA:
  • 2 single-stranded molecules of DNA are intertwined in a double helix.
  • Backbone is made of alternating sugar and phosphate.
  • Held together with a covalent bond.
  • Bases attached to sugars with covalent bonds.
• Antiparallel strands of DNA run in opposite directions so they lie “head-to-toe” with each other.
  • Makes a stable double helix.
  • 5’ → 3’ direction of one strand runs opposite to the other strand (3’-5’).

5’ & 3’ Ends

• A key feature of all nucleic acids is that they have two distinctive ends:
  • the 5' (5-prime) end.
  • the 3' (3-prime) end.
• This terminology refers to the 5' and 3' carbons on the sugar.
• For both DNA and RNA, the 5' end bears a phosphate, and the 3' end a hydroxyl group.

Complementary Base Pairing

• 2-ring purine A pairs with 1-ring pyrimidine T with 2 hydrogen bonds between them.
• 2-ring purine G pairs with 1-ring pyrimidine C with 3 hydrogen bonds between them.

DNA in Our Cells

• We each have about 5-6 feet of DNA in each of our cells.
  • Our bodies have about 744 million miles of DNA in each of us!
• This DNA is organized—packaged—to fit it into the cell’s nucleus.

Chromosomes

• Chromosomes are linear pieces of DNA bound to proteins called histones.
  • We have 46 chromosomes in each cell.
    • 23 from each parent.
  • If the genome is the library of information for the cell, then chromosomes are the books.

Genes

• Genes are segments of DNA that are copied into RNA.
  • A gene is like a recipe in a cookbook.
• Many genes code for making proteins.
  • Humans have 20,000-22,000 genes distributed on our chromosomes.

DNA Replication

• DNA is doubled by exactly copying the bases to make two DNA strands.
  • Occurs in the process of making a new cell.
    • MITOSIS.
  • Basis for biological inheritance.
• For a cell to divide, it must first replicate its DNA.
• The three steps in the process of DNA replication are:
  • Initiation.
  • Elongation.
  • Termination.

DNA Replication Initiation

• During initiation, proteins bind to the origin of replication.
  • Point where replication begins.
• An enzyme called helicase unwinds the DNA helix.
• Two replication forks are formed at the origin of replication.
• The replication forks are extended in both directions as replication proceeds.
  • Creates a replication bubble.
• There are multiple origins of replication on the eukaryotic chromosome.
  • Allows replication to occur simultaneously in hundreds to thousands of locations along each chromosome.

DNA Replication Elongation

• During elongation, an enzyme called DNA polymerase adds DNA nucleotides to the 3' end of the newly synthesized polynucleotide strand.
  • Only the nucleotide complementary to the template nucleotide at that position is added to the new strand.
• DNA polymerase cannot initiate new strand synthesis.
  • Only adds new nucleotides at the 3' end of an existing strand.
• All newly synthesized polynucleotide strands must be initiated by a specialized RNA polymerase called primase.
• Primase initiates polynucleotide synthesis by creating a short RNA polynucleotide strand complementary to the template DNA strand.
  • This short stretch of RNA nucleotides is called the primer.
• Once the RNA primer has been synthesized at the template DNA, primase exits, and DNA polymerase extends the new strand with nucleotides complementary to the template DNA.
• Eventually, the RNA nucleotides in the primer are removed and replaced with DNA nucleotides.
• Once DNA replication is finished, the daughter molecules are made entirely of continuous DNA nucleotides, with no RNA portions.
• DNA polymerase contains a groove that allows it to bind to a single-stranded template DNA and travel one nucleotide at a time.
  • For example, when DNA polymerase meets an adenosine nucleotide on the template strand, it adds a thymidine to the 3' end of the newly synthesized strand, and then moves to the next nucleotide on the template strand.
• This process will continue until the DNA polymerase reaches the end of the template strand.

Leading & Lagging Strands

• DNA polymerase can only synthesize new strands in the 5' to 3' direction.
• Therefore, the two newly-synthesized strands grow in opposite directions because the template strands at each replication fork are antiparallel.
• The leading strand is synthesized continuously toward the replication fork as helicase unwinds the template double-stranded DNA.
• The lagging strand is synthesized in the direction away from the replication fork and away from the DNA helicase unwinds.
  • Synthesized in pieces because the DNA polymerase can only synthesize in the 5' to 3' direction.
  • Constantly encounters the previously-synthesized new strand.
  • The pieces are called Okazaki fragments, and each fragment begins with its own RNA primer.

DNA Replication Termination

• DNA polymerase stops when it reaches a section of the DNA template that has already been replicated.
• However, DNA polymerase cannot catalyze the formation of a phosphodiester bond between the two segments of the new DNA strand, and it drops off.
• These unattached sections of the sugar-phosphate backbone in an otherwise full-replicated DNA strand are called nicks.
• Once all the template nucleotides have been replicated, the replication process is not yet over.
• RNA primers need to be replaced with DNA, and nicks in the sugar-phosphate backbone need to be connected.
• Once the primers are removed, a free-floating DNA polymerase lands at the 3' end of the preceding DNA fragment and extends the DNA over the gap.
• In the final stage of DNA replication, the enzyme ligase joins the sugar-phosphate backbones at each nick site.
• After ligase has connected all nicks, the new strand is one long continuous DNA strand, and the daughter DNA molecule is complete.

Chromosome Structure Eukaryotes vs. Prokaryotes

• Prokaryote:
  • DNA in cytoplasm.
  • Circular chromosome.
  • Single chromosome plus plastids.
  • Made only of DNA.
  • Divides via binary fission.
• Eukaryote:
  • DNA in nucleus.
  • Linear chromosome.
  • Many chromosomes.
  • Made of DNA coiled around histones (=chromatin).
  • Divides by mitosis.

DNA Repair Mechanisms

• DNA repair is a collection of processes by which a cell identifies and corrects damage to DNA.
• In human cells, both normal metabolic activities and environmental factors such as radiation can cause DNA damage.
• As a result, the DNA repair process is constantly active as it responds to damage in the DNA structure.
• When normal repair processes fail, and when cellular apoptosis does not occur, irreparable DNA damage may occur.
• This can eventually lead to malignant tumors or cancer.
• The rate of DNA repair is dependent on many factors including:
  • Cell type.
  • Age of the cell.
  • Extracellular environment.
• A cell that has accumulated a large amount of DNA damage, or one that no longer effectively repairs damage incurred to its DNA, can enter one of three possible states:
  • An irreversible state of dormancy, known as senescence.
  • Cell suicide, also known as apoptosis or programmed cell death.
  • Unregulated cell division, which can lead to the formation of a tumor that is cancerous.
• The DNA repair ability of a cell is vital to the integrity of its genome and thus to the normal functioning of an organism.
  • Many genes that were initially shown to influence lifespan have turned out to be involved in DNA damage repair and protection.

Mutations

• Mutations are changes on the DNA usually involving only 1 to 10 bases.
• Since every 3 bases on the gene of the DNA codes for an amino acid, then a change in bases on the gene DNA can change the protein.
• Mutations usually occur when there is an error in cell division following meiosis or mitosis.
  • May affect the function of the protein coded for.
• There are many types of mutations.

Types of Mutations

• Missense Mutation:
  • This type of mutation is a change in one DNA base pair that results in the substitution of one amino acid for another in the protein made by a gene.
    • Sickle cell anemia.
• Nonsense Mutation:
  • Also a change in one DNA base pair.
  • Instead of substituting one amino acid for another, the altered DNA sequence prematurely signals the cell to stop building a protein.
  • Results in a shortened protein that may function improperly or not at all.
• Insertion:
  • Changes the number of DNA bases in a gene by adding a piece of DNA.
    • Polydactyly.
• Deletion:
  • Changes the number of DNA bases by removing a piece of DNA.
  • Small deletions may remove one or a few base pairs within a gene, while larger deletions can remove an entire gene or several neighboring genes.
    • Cri du chat syndrome: Part of chromosome 5 is deleted; its name is a French term referring to the characteristic cat-like cry of affected children.
• Duplication:
  • A duplication consists of a piece of DNA that is abnormally copied one or more times.
  • Duplication mutations can create genetic redundancy, which can lead to evolutionary innovation.
    • Down syndrome, also known as trisomy 21, is a disease caused by an extra copy of chromosome 21, which can result in developmental delays and other abnormalities. Most cases of Down syndrome are not inherited but instead occur by a random error during cell division.
• Frameshift Mutation:
  • Occurs when the addition or loss of DNA bases changes a gene's reading frame.
    • A reading frame consists of groups of 3 bases that each code for one amino acid.
  • A frameshift mutation shifts the grouping of these bases and changes the code for amino acids.
  • Insertions, deletions, and duplications can all be frameshift mutations. Insertions and deletions are examples of frameshift mutations.
• Repeat Expansion:
  • Short DNA sequences are repeated a number of times in a row.
  • Can cause a number of inherited neurological conditions.
    • Fragile X syndrome (FXS) is a genetic disorder that affects a person's development and can cause intellectual disability. Most commonly found in males.