DNA Structure and Chromosomes

Lecture 3.2: DNA Structure & Chromosomes

Objectives

• Define and use correctly:

  • Genotype

  • Phenotype

  • Homozygous

  • Heterozygous

  • Alleles

  • 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 four groups of biomolecules.

  • Monomers: Nucleotides

  • Polymers: Polynucleotides

• Major nucleic acids:

  • DNA (deoxyribonucleic acid)

    • Stores genetic information in all cells.

    • Very large (about 10 billion atoms).

    • Inherit half from each parent.

  • RNA (ribonucleic acid)

    • Necessary for converting DNA’s information into proteins.

    • Several types of RNA exist.

Nucleotides: Monomers of Nucleic Acids

• Composed 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 $-OPO3^-$.

  • A nitrogenous base:

    • A ring structure containing carbon and at least 2 nitrogen atoms.

    • May be a double or single ring.

Structure of Nucleotides

• Includes a phosphate group, deoxyribose sugar, and a nitrogenous base (adenine).

Names of Nitrogenous Bases

• Bases with 1 ring (Pyrimidines):

  • Thymine (T)

  • Cytosine (C)

  • Uracil (U)

Names of Nitrogenous Bases

• Bases with 2 rings (Purines):

  • Adenine (A)

  • Guanine (G)

Names of Nitrogenous Bases

• 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.

Sugars on DNA and RNA

• The "R" in RNA stands for "ribo."

• Ribose sugar with its oxygen.

Sugars on DNA and RNA - Differences

• Deoxyribose has one less oxygen atom than ribose.

Nucleic Acids Are Polymers of Nucleotides

• DNA consists of 2 strands of nucleic acids wrapped in a double helix.

• RNA is single-stranded.

Nucleic Acids Are Polymers of Nucleotides

• Nucleotides form nucleic acids via dehydration reaction.

  • Removing water forms a covalent bond between the phosphate of one nucleotide and the sugar of the second nucleotide.

Nucleic Acids Are Polymers of Nucleotides

• Single-stranded nucleic acids (RNA):

  • Backbone: alternating sugar and phosphate.

  • Held together with a covalent bond.

  • Bases attached to sugar with covalent bonds.

Nucleic Acids Are Polymers of Nucleotides

• Double-stranded nucleic acids (DNA):

  • 2 single-stranded molecules intertwined in a double helix.

  • Backbone: alternating sugar and phosphate.

  • Held together with a covalent bond.

  • Bases attached to sugars with covalent bonds.

Nucleic Acids Are Polymers of Nucleotides

• Antiparallel strands of DNA run in opposite directions.

  • 5’ → 3’ direction of one strand runs opposite to the other strand (3’-5’).

5’ & 3’ Ends

• Nucleic acids have two distinctive ends: the 5' (5-prime) end and 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

• The 2-ring purine Adenine (A) pairs with the 1-ring pyrimidine Thymine (T) with 2 hydrogen bonds.

• The 2-ring purine Guanine (G) pairs with the 1-ring pyrimidine Cytosine (C) with 3 hydrogen bonds.

DNA in Our Cells

• Each cell contains about 5-6 feet of DNA.

  • The body has about 744 million miles of DNA.

• DNA is organized and packaged to fit into the cell’s nucleus.

Chromosomes

• Chromosomes are linear pieces of DNA bound to proteins called histones.

  • Humans have 46 chromosomes in each cell (23 from each parent).

• If the genome is the library of information, 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 chromosomes.

DNA Replication

• DNA is doubled by exactly copying the bases to make two DNA strands.

  • Occurs during cell division (MITOSIS).

  • Basis for biological inheritance.

DNA Replication

• 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.

  • The point where replication begins.

• Helicase unwinds the DNA helix.

• Two replication forks are formed at the origin of replication.

DNA Replication Initiation

• Replication forks extend in both directions.

  • Creating a replication bubble.

• Multiple origins of replication exist on the eukaryotic chromosome.

  • Allows replication to occur simultaneously in hundreds to thousands of locations along each chromosome.

DNA Replication Elongation

• During elongation, 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 Replication Elongation

• 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.

DNA Replication Elongation

• Primase initiates polynucleotide synthesis by creating a short RNA polynucleotide strand complementary to template DNA strand.

  • This short stretch of RNA nucleotides is called the primer.

• Once 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.

DNA Replication Elongation

• 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 Replication Elongation

• 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 continues 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.

Leading & Lagging Strands

• The lagging strand is synthesized in the direction away from the replication fork and away from where 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 fully replicated DNA strand are called nicks.

DNA Replication Termination

• 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.

DNA Replication Termination

• 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.

DNA Replication Termination

• 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 plasmids.

  • 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.

DNA Repair Mechanisms

• 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 as per the two currently accepted hypotheses.

DNA Repair Mechanisms

• 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

DNA Repair Mechanisms

• 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 life span 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

• 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

• 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.

  • Example: Sickle cell anemia.

Types of Mutations: Nonsense Mutation

• 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.

Types of Mutations: Insertion

• Changes the number of DNA bases in a gene by adding a piece of DNA.

  • Example: Polydactyly.

Types of Mutations: 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.

  • Example: Cri du chat syndrome (part of chromosome 5 is deleted).

Types of Mutations: 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.

  • Example: Down syndrome (trisomy 21), caused by an extra copy of chromosome 21.

    • Most cases are not inherited but occur by a random error during cell division.

Types of Mutations: 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.

Types of Mutations: Repeat Expansion

• Short DNA sequences are repeated a number of times in a row.

• Can cause a number of inherited neurological conditions.

  • Example: Fragile X syndrome (FXS).

    • A genetic disorder that affects a person's development and can cause intellectual disability.

    • Most commonly found in males.

NEXT

Mendel & the Gene Idea

Patterns of Inheritance