CHAPTER 10
The Nature of the Gene
and the Genome
Introduction
• Hereditary factors consist of DNA and
reside on chromosomes.
• The collective body of genetic information
in an organism is called the genome.
Overview of early discoveries on the nature
of the gene
10.1 The Concept of a Gene as a
Unit of Inheritance (1)
• Mendel’s work
became the
foundation for the
science of
genetics.
• He established
the laws of
inheritance based
on his studies of
pea plants.
The Concept of a Gene as a Unit of
Inheritance (2)
1. Characteristics of organisms are
governed by units of inheritance called
genes.
a) Each trait is controlled by two forms of a
gene called alleles.
b) Alleles could be identical or nonidentical.
c) When alleles are nonidentical, the dominant
allele masks the recessive allele.
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).
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.
Cellular process in the roundworm
following fertilization
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
Mendel’s laws of inheritance.
Homologous chromosomes
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.
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.
Drosophila as a genetic tool
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.
Crossing over in Drosophila
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.
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.
Polytene chromosomes
10.3 The Chemical Nature
of 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).
The chemical structure of DNA
The chemical structure
of DNA
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.
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]
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.
The double helix
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.
The double helix (continued)
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.
Three functions of the genetic material
The Chemical Nature of the Gene
(7)
• DNA Supercoiling
– DNA that is more
compact than its
relaxed counterpart is
called supercoiled.
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.
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.
DNA topoisomerases
DNA topoisomerases
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).
The Structure of the Genome (2)
• DNA Renaturation
– Renaturation or reanneling is when singlestranded 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.
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.
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
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.
DNA fingerprinting
Fluorescence in situ hybridization and
localization of satellite DNA
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.
Chromosomal localization
of nonrepeated DNA
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.
Trinucleotide repeat sequences
and human disease
The Human Perspective: Diseases That Result
from Expansion of Trinucleotide Repeats (2)
• Huntington’s 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).
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.
A sample of agricultural crops
that are polyploid
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.
Unequal crossing over between
duplicated genes
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.
A pathway for the
evolution of globin
genes
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.
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.
Transposition in bacteria
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.
Pathways in the movement
of transposable elements
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
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.
Genome comparisons
Sequencing Genomes: The Footprints
of Biological Evolution (2)
• Comparative Genomics: “If It’s 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
Small segments of DNA are highly conserved
between humans and related species
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.
Duplication of the amylase gene during
human evolution
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).
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 intermediatesized variants are more common than
previously thought.
Structural variants
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.
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.
The genome is divided into haplotypes
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.
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.
Outline of Griffith’s experiment
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.
Bacterial infection of the T4 bacteriophage
The Hershey-Chase experiment