Chapter 4

The Content of
the Genome
 4.1 Introduction

• genome – The complete set of sequences in the

genetic material of an organism.
– It includes the sequence of each chromosome
plus any DNA in organelles.
• transcriptome – The complete set of RNAs
present in a cell, tissue, or organism.
– Its complexity is due mostly to mRNAs, but it also
includes noncoding RNAs.
 4.1 Introduction

• proteome – The complete set of proteins that is

expressed by the entire genome.
– The term is sometimes used to describe the
complement of proteins expressed by a cell at
any one time.
• interactome – The complete set of protein
complexes/protein–protein interactions present
in a cell, tissue, or organism.
4.2 Genome Mapping Reveals That Individual
Genomes Show Extensive Variation
• Linkage maps are based on the frequency of
recombination between genetic markers.
• Restriction maps are based on the physical
distances between markers.
• Genomes are mapped by sequencing their DNA
and identifying functional genes.
4.2 Genome Mapping Reveals That Individual
Genomes Show Extensive Variation
• Polymorphism can be detected at the phenotypic
level when a sequence affects gene function, at the
restriction fragment level when it affects a restriction
enzyme target site, and at the sequence level by
direct analysis of DNA.
• The alleles of a gene show extensive polymorphism
at the sequence level, but many sequence changes
do not affect function.
4.2 Genome Mapping Reveals That Individual
Genomes Show Extensive Variation
• single nucleotide polymorphism (SNP) – A
polymorphism (variation in sequence between
individuals) caused by a change in a single
nucleotide.
– SNPs are responsible for most of the genetic
variation between individuals.
 4.3 SNPs Can Be Associated with
Genetic Disorders
• Through genome wide association studies,
researchers can identify SNPs that are more
frequently found in patients with a particular
disorder.
• haplotype – The particular combination of alleles in
a defined region of some chromosome; in effect, the
genotype in miniature.
– Originally used to describe combinations of major
histocompatibility complex (MHC) alleles, it now may
be used to describe particular combinations of
RFLPs, SNPs, or other markers.
4.3 SNPs Can Be Associated with
Genetic Disorders
Figure 4.1: In a genome wide
association study, both
patients and nonpatient
controls for a particular
disorder (such as heart
disease, schizophrenia, or a
single-gene disorder) are
screened for SNPs across their
genomes. Those SNPs that are
statistically more frequently
found in patients than in
nonpatients can be identified.
 4.3 SNPs Can Be Associated with
Genetic Disorders
• DNA profiling – A technique for analyzing the
differences between individuals of the fragments
generated by using restriction enzymes to cleave
regions that contain short repeated sequences, or
by PCR.
– The lengths of the repeated regions are unique to
every individual.
– The presence of a particular subset in any two
individuals can be used to define their common
inheritance (e.g., a parent–child relationship).
 4.4 Eukaryotic Genomes Contain
Nonrepetitive and Repetitive DNA Sequences
• The kinetics of DNA reassociation after a genome
has been denatured distinguish sequences by their
frequency of repetition in the genome.
• Polypeptides are generally encoded by sequences
in nonrepetitive DNA.
• Larger genomes within a taxonomic group do not
contain more genes but have large amounts of
repetitive DNA.
 4.4 Eukaryotic Genomes Contain
Nonrepetitive and Repetitive DNA Sequences
• A large part of
moderately repetitive
DNA can be made
up of transposons.

Figure 4.2: The proportions of

different sequence components
vary in eukaryotic genomes.
4.5 Eukaryotic Protein-Coding Genes Can Be
Identified by the Conservation of Exons and of
Genome Organization
• Researchers can use the conservation of exons as
the basis for identifying coding regions by identifying
fragments whose sequences are present in multiple
organisms.
• Methods for identifying functional genes are not
perfect and many corrections must be made to
preliminary estimates.
• Pseudogenes must be distinguished from functional
genes.
4.5 Eukaryotic Protein-Coding Genes Can Be
Identified by the Conservation of Exons and of
Genome Organization

Figure 4.3: Exons of protein-coding genes are identified as coding

sequences flanked by appropriate signals.
4.5 Eukaryotic Protein-Coding Genes Can Be
Identified by the Conservation of Exons and of
Genome Organization
• There are extensive syntenic relationships between
the mouse and human genomes, and most
functional genes are in a syntenic region.
• synteny – A relationship between chromosomal
regions of different species where homologous
genes occur in the same order.

Figure 4.4: Mouse chromosome

1 has 21 segments 1-25 Mb in
length syntenic with regions
corresponding to parts of six
human chromosomes.
4.5 Eukaryotic Protein-Coding Genes Can Be
Identified by the Conservation of Exons and of
Genome Organization
• expressed sequence tag (EST) – A short
sequenced fragment of a cDNA sequence that can
be used to identify an actively expressed gene.
 4.6 Some Eukaryotic
Organelles Have DNA
• Mitochondria and
chloroplasts have genomes
that show non-Mendelian
inheritance. Typically they
are maternally inherited.
• Organelle genomes can
undergo somatic segregation
in plants.

Figure 4.6: In animals, DNA from the

sperm enters the oocyte to form the male
pronucleus in the egg, but all the
mitochondria are provided by the oocyte.
 4.6 Some Eukaryotic
Organelles Have DNA
• extranuclear genes – Genes that reside outside
the nucleus, in organelles such as mitochondria and
chloroplasts.
• Comparisons of human mitochondrial DNA suggest
that it is descended from a single population that
existed approximately 200,000 years ago in Africa.
4.7 Organelle Genomes Are Circular DNAs
That Encode Organelle Proteins
• Organelle genomes are usually (but not always)
circular molecules of DNA.
– Mitochondrial DNA (mtDNA)
– Chloroplast DNA (cpDNA or ctDNA)
• Organelle genomes encode some, but not all, of the
proteins used in the organelle.

Table 4.1: Mitochondrial

genomes have genes
encoding (mostly
complex I–IV) proteins,
rRNAs, and tRNAs.
4.7 Organelle Genomes Are Circular DNAs
That Encode Organelle Proteins
• Animal cell mtDNA is extremely compact and
typically encodes 13 proteins, 2 rRNAs, and 22
tRNAs.
• D loop – A region of the animal mitochondrial DNA
molecule that is variable in size and sequence and
contains the origin of replication.
• Yeast mtDNA is five times longer than animal cell
mtDNA because of the presence of long introns.
4.7 Organelle Genomes Are Circular DNAs
That Encode Organelle Proteins

Figure 4.7: Human mitochondrial

DNA has 22 tRNA genes, two rRNA
genes, and 13 protein-coding
regions.
4.8 The Chloroplast Genome Encodes
Many Proteins and RNAs
• Chloroplast genomes
vary in size, but are
large enough to
encode 50 to 100
proteins as well as the
rRNAs and tRNAs.

Table 4.2: The chloroplast

genome in land plants
encodes 4 rRNAs, 30 tRNAs,
and ~60 proteins.
4.9 Mitochondria and Chloroplasts
Evolved by Endosymbiosis
• Both mitochondria and
chloroplasts are descended
from bacterial ancestors.
• Most of the genes of the
mitochondrial and chloroplast
genomes have been transferred
to the nucleus during the
organelle’s evolution.

Figure 4.9: Mitochondria originated by a

endosymbiotic event when a bacterium was
captured by a eukaryotic cell.