The Nature of the Gene

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CHAPTER 10

• The Nature of the Gene
• and the Genome

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Introduction

• Hereditary factors consist of DNA and reside on
  chromosomes.
• The collective body of genetic information in an
  organism is called the genome.

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Overview of early discoveries on the nature of
the gene
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10.1 The Concept of a Gene as a Unit of
Inheritance (1)

• Mendels work became the foundation for the
  science of genetics.
• He established the laws of inheritance based on
  his studies of pea plants.

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The Concept of a Gene as a Unit of Inheritance (2)

• Characteristics of organisms are governed by
  units of inheritance called genes.
• Each trait is controlled by two forms of a gene
  called alleles.
• Alleles could be identical or nonidentical.
• When alleles are nonidentical, the dominant
  allele masks the recessive allele.

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The Concept of a Gene as a Unit of Inheritance (3)

• 2. A reproductive cell (gamete) contains one gene
  for each trait.
• a) Somatic cells arise by the union of male
  and
• female gametes.
• b) Two alleles controlling each trait are
  inherited one
• from each parent.
• 3. The pairs of genes are separated (segregated)
  during gamete formation.
• 4. Genes controlling different traits segregate
  independently of each (independent assortment).

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10.2 Chromosomes The Physical Carriers of Genes
(1)

• The Discovery of Chromosomes
• Chromosomes were first observed in dividing
  cells, using the light microscope.
• Chromosomes are divided equally between the two
  daughter cells during cell division.
• Chromosomes are doubled prior to cell division.

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Cellular process in the roundwormfollowing
fertilization
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Chromosomes The Physical Carriers of Genes (2)

• Chromosomes as the Carriers of Genetic
  Information
• Chromosomes are present as pairs of homologous
  chromosomes.
• During meiosis, homologous chromosomes associate
  and form a bivalent then separate into different
  cells.
• Chromosomal behavior correlates with Mendels
  laws of inheritance.

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Homologous chromosomes
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Chromosomes The Physical Carriers of Genes (3)

• The chromosome as a linkage group
• Genes that are on the same chromosome do not
  assort independently.
• Genes on the same chromosome are part of the same
  linkage group.
• The traits analyzed by Mendel occur on different
  chromosomes.

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Chromosomes The Physical Carriers of Genes (4)

• Genetic Analysis in Drosophila
• Morgan was the first to use fruit flies in
  genetic research.
• Morgan only had available wild type flies but one
  he developed his first mutant, it became a
  primary tool for genetic research.
• Mutation was recognized as a mechanism for
  variation in populations.
• Studies with Drosophila confirmed that genes
  reside on chromosomes.

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Drosophila as a genetic tool
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Chromosomes The Physical Carriers of Genes (5)

• Crossing Over and Recombination
• Linkage between alleles on the same chromosome is
  incomplete.
• Maternal and paternal chromosomes can exchange
  pieces during crossing over or genetic
  recombination.

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Crossing over in Drosophila
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Chromosomes The Physical Carriers of Genes (6)

• Crossing over and recombination
• Percentage of recombination between a pair of
  genes is constant.
• Percentage of recombination between different
  pairs of genes can be different.
• The positions of genes along the chromosome
  (loci) can be mapped.
• Frequency of recombination indicates distance,
  and increases as distance increases.

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Chromosomes The Physical Carriers of Genes (7)

• Mutagenesis and Giant Chromosomes
• Exposure to a sublethal dose of X-rays increases
  the rate of spontaneous mutations.
• Cells from the salivary gland of Drosophila have
  giant polytene chromosomes.
• Polytene chromosomes have been useful to observe
  specific bands correlated with individual genes.
• Puffs in polytene chromosomes allow
  visualization of gene expression.

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Polytene chromosomes
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10.3 The Chemical Natureof the Gene (1)

• DNA is the genetic material in all organisms.
• The Structure of DNA
• The nucleotide is the building block of DNA.
• It consists of a phosphate, a sugar, and either a
  pyrimidine or purine nitrogenous base.
• There are two different pyrimidines thymine (T)
  and cytosine (C).
• There are two different purines adenine (A) and
  guanine (G).

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The chemical structure of DNA
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The chemical structureof DNA
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The Chemical Nature of the Gene (2)

• Nucleotides have a polarized structure where the
  ends are called 5 and 3 .
• Nucleotides are linked into nucleic acids
  polymers
• Sugar and phosphates are linked by
  3,5-phosphodiester bonds.
• Nitrogenous bases project out like stacked
  shelves.

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The Chemical Nature of the Gene (3)

• Chargaff established rules after doing base
  composition analysis
• Number of adenine number of thymine
• Number of cytosine number of guanine
• A T ? G C

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The Chemical Nature of the Gene (4)

• The Watson-Crick Proposal
• The DNA molecule is a double helix.
• DNA is composed of two chains of nucleotides.
• The two chains spiral around each other forming a
  pair of right-hand helices.
• The two chains are antiparallel, they run in
  opposite directions.
• The sugar-phosphate backbone is located on the
  outside of the molecule.
• The bases are inside the helix.

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The double helix
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The Chemical Nature of the Gene (5)

• The Watson-Crick Proposal (continued)
• The DNA is a double helix
• The two DNA chains are held together by hydrogen
  bonds between each base.
• The double helix is 2 nm wide.
• Pyrimidines are always paired with purines.
• Only A-T and C-G pairs fit within double helix.
• Molecule has a major groove and a minor groove.
• The double helix makes a turn every 10 residues.
• The two chains are complementary to each other.

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The double helix (continued)
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The Chemical Nature of the Gene (6)

• The Importance of the Watson-Crick Proposal
• Storage of genetic information.
• Replication and inheritance.
• Expression of the genetic message.

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Three functions of the genetic material
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The Chemical Nature of the Gene (7)

• DNA Supercoiling
• DNA that is more compact than its relaxed
  counterpart is called supercoiled.

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The Chemical Nature of the Gene (8)

• DNA Supercoiling (continued)
• Underwound DNA is negatively supercoiled, and
  overwound DNA is positively supercoiled.
• Negative supercoiling plays a role in allowing
  chromosomes to fit within the cell nucleus.

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The Chemical Nature of the Gene (9)

• DNA Supercoiling (continued)
• Enzymes called topoisomerases change the level of
  DNA supercoiling.
• Cells contain a variety of topoisomerases.
• Type I change the supercoiled state by creating
  a transient break in one strand of the duplex.
• Type II make a transient break in both strands
  of the DNA duplex.

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DNA topoisomerases
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DNA topoisomerases
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10.4 The Structure of the Genome (1)

• The genome of a cell is its unique content of
  genetic information.
• The Complexity of the Genome
• One important property of DNA is its ability to
  separate into two strands (denaturation).

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The Structure of the Genome (2)

• DNA Renaturation
• Renaturation or reanneling is when
  single-stranded DNA molecules are capable of
  reassociating.
• Reanneling has led to the development of nucleic
  acid hybridization in which complementary strands
  of nucleic acids form different sources can form
  hybrid molecules.

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The Structure of the Genome (3)

• The Complexity of Viral and Bacterial Genomes
• The rate of renaturation of DNA from bacteria and
  viruses depends on the size of their genome.

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The Structure of the Genome (4)

• The Complexity of the Eukaryotic Genome
• Reanneling of eukaryotic genomes shows three
  classes of DNA
• Highly repeated
• Moderately repeated
• Nonrepeated

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The Structure of the Genome (5)

• Highly Repeated DNA Sequences represent about
  1-10 of total DNA.
• Satellite DNAs short sequences that tend to
  evolve very rapidly.
• Minisatellite DNAs unstable and tend to be
  variable in the population form the basis of DNA
  fingerprinting.
• Microsatellite DNAs shortest sequences and
  typically found in small clusters implicated in
  genetic disorders.

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DNA fingerprinting
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Fluorescence in situ hybridization and
localization of satellite DNA
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The Structure of the Genome (6)

• Moderately Repeated DNA Sequences
• Repeated DNA Sequences with Coding Functions
  include genes that code for ribosomal RNA and
  histones.
• Repeated DNA Sequences that Lack Coding Functions
  do not include any type of gene product can be
  grouped into two classes SINEs or LINEs.
• Nonrepeated DNA Sequences code for the majority
  of proteins.

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Chromosomal localizationof nonrepeated DNA
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The Human Perspective Diseases That Result from
Expansion of Trinucleotide Repeats (1)

• Mutations occur in genes containing a repeating
  unit of three nucleotides.
• The mutant alleles are highly unstable and the
  number of repeating units tends to increase as
  the gene passes from parent to offspring.
• Type I disease are all neurodegenerative
  disorders resulting form expansion of CAG
  trinucleotides.

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Trinucleotide repeat sequencesand human disease
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The Human Perspective Diseases That Result from
Expansion of Trinucleotide Repeats (2)

• Huntingtons disease (HD) result from 36
  glutamine repeats in the huntingtin gene.
• The molecular basis of HD remains unclear but it
  is presumed that expanded glutamine repeats are
  toxic to brain cell.
• Type II diseases arise from a variety of
  trinucleotide repeats, and are present in parts
  of the gene that do not code for amino acids
  (i.e. fragile X syndrome).

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10.5 The Stability of the Genome (1)

• Whole Genome Duplication (Polyploidization)
• Polyploidization (or whole genome duplication)
  occurs when offspring receive more than two sets
  of chromosomes from their parents.
• Could be the result of hybrids from closely
  related parents.
• Could result from duplicate chromosomes not
  separated in embryonic cells.

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A sample of agricultural cropsthat are polyploid
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The Stability of the Genome (2)

• Duplication and Modification of DNA Sequences
• Gene duplication occurs within a portion of a
  single chromosome.
• Duplication may occur by unequal crossing over
  between misaligned homologous chromosomes.
• Duplication has played a major role in the
  evolution of multigene families.

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Unequal crossing over betweenduplicated genes
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The Stability of the Genome (3)

• Evolution of Globin Genes
• The globin gene family includes hemoglobin,
  myoglobin, and plant leghemoglobin.
• Ancestral forms have given rise to recent forms
  by duplication, gene fusion, and divergence.
• Some sequences, called pseudogenes, resemble
  globin genes but are nonfunctional.

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A pathway for the evolution of globin genes
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The Stability of the Genome (4)

• Jumping Genes and the Dynamic Nature of the
  Genome
• Genetic elements are capable of moving within a
  chromosome (transposition).
• Those mobile elements are called transposable
  elements.

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The Stability of the Genome (5)

• Transposition
• Only certain sequences can acts as transposons,
  but these insert into target sites randomly.
• It requires the enzyme transposase to facilitate
  insertion of transposons into target site.
• Bacterial trasnposition occurs by replication of
  the transposable element, followed by insertion.

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Transposition in bacteria
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The Stability of the Genome (6)

• Transposition (continued)
• Integration of the element creates a small
  duplication in target DNA, which serves as a
  footprint to identify sites occupied by
  transposable elements.
• Retrotransposons use an RNA intermediate which
  produces a complementary DNA via reverse
  transcriptase viruses such as HIV use this
  mechanism to replicate their genome.

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Pathways in the movementof transposable elements
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The Stability of the Genome (7)

• The Role of Mobile Genetic Elements in Evolution
• Some moderately repeated sequences in human DNA
  (Alu and L1) are transposable elements.
• Possible evolutionary roles
• Rearrangement of the genome
• Regulation of gene expression
• Production of new genes

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10.6 Sequencing Genomes The Footprints of
Biological Evolution (1)

• The genomes of hundreds of organisms have been
  sequenced.
• In 2004 the finished version of the human
  genome was reported.
• It contains about 20,000 genes.
• Alternate splicing of messenger RNA may account
  for several proteins from one gene.
• Post-translational modifications also account for
  different protein functions.

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Genome comparisons
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Sequencing Genomes The Footprints of Biological
Evolution (2)

• Comparative Genomics If Its Conserved, It Must
  Be Important
• DNA that is similar among related organisms is
  considered to be important, even when the precise
  role is still unclear.
• Some important DNA in humans may have a recent
  origin

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Small segments of DNA are highly conserved
between humans and related species
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Sequencing Genomes The Footprints of Biological
Evolution (3)

• The Genetic Basis of Being Human
• By focusing on conserved sequence, we can learn
  about traits we share with other species.
• The gene FOXP2 in human differs very little from
  that in chimps, and is called the speech gene.
• Another gene is HAR1, which also differ little
  between humans and chimps and its function is
  unknown.
• The gene AMY1 encodes the enzyme amylase and its
  frequency is remarkably different between humans
  and chimps.

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Duplication of the amylase gene during human
evolution
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Sequencing Genomes The Footprints of Biological
Evolution (4)

• Genetic Variation within the Human Species
  Population
• The genome varies among different individuals due
  to genetic polymorphisms.
• DNA Sequence Variation
• The most common variability among humans is at
  the single nucleotide difference.
• These sites are called single nucleotide
  polymorphisms (SNPs).

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Sequencing Genomes The Footprints of Biological
Evolution (5)

• Structural Variation
• Segments of the genome can change, and these
  changes may involve large segments of the DNA
  (structural variants).
• Recent studies indicate that intermediate-sized
  variants are more common than previously thought.

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Structural variants
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The Human Perspective Application of Genomic
Analysis to Medicine (1)

• Until recently, the gene responsible for a
  disease was identified through traditional
  genetic linkage studies.
• However, the low penetrance of most genes for
  common diseases cannot be identified through
  family linkage studies.
• Genome-wide association studies look for links
  between a disease and polymorphisms located in
  the genome.

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The Human Perspective Application of Genomic
Analysis to Medicine (2)

• SNPs may play an important role is susceptibility
  to disease or act as genetic markers for
  susceptibility.
• SNPs can be inherited in blocks called
  haplotypes.
• Haplotype maps (HapMaps) are based on common
  haplotypes.
• HapMaps may lead to associations between disease
  and haplotypes.

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The genome is divided into haplotypes
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Experimental Pathways The Chemical Nature of the
Gene (1)

• The nature of the gene was discovered through a
  series of unrelated studies.
• Miescher first identified nuclein in white
  blood cell extracts and in salmon sperm.
• Levene proposed the tetranucleotide theory,
  indicating that DNA was a boring repetition of
  four nucleotides and could not be the genetic
  material.

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Experimental Pathways The Chemical Nature of the
Gene (2)

• Griffith carried out experiments with
  pneumococcus bacteria with different abilities
  to cause disease.
• He observed transformation in bacteria caused by
  a transforming principle.

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Outline of Griffiths experiment
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Experimental Pathways The Chemical Nature of the
Gene (3)

• Further experiments by Avery, MacLeod, and
  McCarty led to the conclusion that DNA was the
  transforming principle.
• Experiments done by Hershey and Chase using a
  bacteriophage confirmed that DNA and not protein
  is the genetic material.

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Bacterial infection of the T4 bacteriophage
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The Hershey-Chase experiment