Chapter 7
Clusters and
Repeats
7.1 Introduction
• gene family – A set of genes within a genome
that encode related or identical proteins or
RNAs.
– The members were derived by duplication of an
ancestral gene followed by accumulation of changes
in sequence between the copies.
– Most often the members are related but not identical.
7.1 Introduction
• pseudogenes – Inactive but stable components
of the genome derived by mutation of an
ancestral active gene.
– Usually they are inactive because of mutations that
block transcription or translation or both.
• gene cluster – A group of adjacent genes that
are identical or related.
7.1 Introduction
Figure 07.01: Chiasma formation can result in the generation of recombinants.
7.1 Introduction
Figure 07.02: Recombination involves pairing between complementary strands of the two
parental duplex DNAs.
7.1 Introduction
• unequal crossing over
(nonreciprocal
recombination) – Unequal
crossing over results from
an error in pairing and
crossing over in which
nonequivalent sites are
involved in a recombination
event.
– It produces one recombinant
with a deletion of material
and one with a duplication.
Figure 07.03: Unequal crossing
over results from pairing between
nonequivalent repeats in regions
of DNA consisting of repeating
units.
7.1 Introduction
• satellite DNA – DNA that consists of
many tandem repeats (identical or related)
of a short basic repeating unit.
7.1 Introduction
• minisatellite – DNAs consisting of tandemly
repeated copies of a short repeating sequence,
with more repeat copies than a microsatellite but
fewer than a satellite.
– The length of the repeating unit is measured in tens of
base pairs.
– The number of repeats varies between individual
genomes.
7.2 Unequal Crossing Over Rearranges
Gene Clusters
• When a genome contains a cluster of genes with
related sequences, mispairing between
nonallelic loci can cause unequal crossing over.
– This produces a deletion in one recombinant
chromosome and a corresponding duplication in the
other.
7.2 Unequal Crossing Over Rearranges
Gene Clusters
Figure 07.04: Gene number can be changed by unequal crossing over.
7.2 Unequal Crossing Over Rearranges
Gene Clusters
• Different thalassemias are
caused by various deletions
that eliminate α- or β-globin
genes.
– The severity of the disease
depends on the individual
deletion.
Figure 07.05: α-thalassemias result
from various deletions in the αglobin gene cluster.
7.2 Unequal Crossing Over Rearranges
Gene Clusters
Figure 07.06: Deletions in the ß-globin gene cluster cause several types of thalassemia.
7.2 Unequal Crossing Over Rearranges
Gene Clusters
• HbH disease – A condition in which there is a
disproportionate amount of the abnormal tetramer β4
relative to the amount of normal hemoglobin (α2β2).
• hydrops fetalis – A fatal disease resulting from the
absence of the hemoglobin α gene.
7.2 Unequal Crossing Over Rearranges
Gene Clusters
• Hb Lepore – An unusual globin protein that
results from unequal crossing over between the
β and δ genes.
– The genes become fused together to produce a
single β-like chain that consists of the N-terminal
sequence of δ joined to the C-terminal sequence of β.
7.2 Unequal Crossing Over Rearranges
Gene Clusters
• Hb anti-Lepore – A fusion gene produced by unequal
crossing over that has the N-terminal part of β globin and
the C-terminal part of δ globin.
• Hb Kenya – A fusion gene produced by unequal
crossing over between the Aγ- and β-globin genes.
7.3 Genes for rRNA Form Tandem Repeats
Including an Invariant Transcription Unit
• Ribosomal RNA is encoded by a large number of
identical genes that are tandemly repeated to form one
or more clusters.
• Each rDNA cluster is organized so that transcription
units giving a joint precursor to the major rRNAs
alternate with nontranscribed spacers.
• The genes in an rDNA cluster all have an identical
sequence.
7.3 Genes for rRNA Form Tandem Repeats
Including an Invariant Transcription Unit
• The nontranscribed
spacers consist of shorter
repeating units whose
number varies so that the
lengths of individual
spacers are different.
Figure 07.07: A tandem gene cluster has an
alternation of transcription unit and
nontranscribed spacer and generates a
circular restriction map.
7.3 Genes for rRNA Form Tandem Repeats
Including an Invariant Transcription Unit
• nucleolus – A discrete region of the nucleus where
ribosomes are produced.
• nucleolar organizer – The region of a chromosome
carrying genes encoding rRNA.
7.3 Genes for rRNA Form Tandem Repeats
Including an Invariant Transcription Unit
• Bam islands – A series of short repeated sequences
found in the nontranscribed spacer of Xenopus rDNA
genes.
Figure 07.10: The nontranscribed spacer of X. laevis rDNA has an internally repetitious
structure that is responsible for its variation in length.
7.4 Crossover Fixation Could Maintain
Identical Repeats
• Unequal crossing over changes the size of a cluster of
tandem repeats.
• Individual repeating units can be eliminated or can
spread through the cluster.
• concerted evolution (coincidental evolution) – The
ability of two or more related genes to evolve together as
though constituting a single locus.
7.4 Crossover Fixation Could Maintain
Identical Repeats
• gene conversion – The alteration of one strand of a
heteroduplex DNA to make it complementary with the
other strand at any position(s) where there were
mispaired bases.
• crossover fixation – A possible consequence of
unequal crossing over that allows a mutation in one
member of a tandem cluster to spread through the whole
cluster (or to be eliminated).
7.4 Crossover Fixation Could Maintain
Identical Repeats
Figure 07.11: Unequal recombination
allows one particular repeating unit to
occupy the entire cluster.
7.5 Satellite DNAs Often Lie in
Heterochromatin
• Highly repetitive DNA (or
satellite DNA) has a very
short repeating sequence and
no coding function.
• simple sequence DNA –
Short repeating units of DNA
sequence.
• Satellite DNA occurs in large
blocks that can have distinct
physical properties.
Figure 07.12: Mouse DNA is separated
into a main band and a satellite band
by centrifugation through a density
gradient of CsCl.
7.5 Satellite DNAs Often Lie in
Heterochromatin
• cryptic satellite – A satellite DNA sequence not
identified as such by a separate peak on a
density gradient.
– It remains present in main-band DNA.
7.5 Satellite DNAs Often Lie in
Heterochromatin
• in situ hybridization –
Hybridization performed
by denaturing the DNA of
cells squashed on a
microscope slide so that
reaction is possible with
an added single-stranded
RNA or DNA.
– The added preparation is
radioactively labeled and
its hybridization is followed
by autoradiography.
Figure 07.13: Cytological hybridization
shows that mouse satellite DNA is
located at the centromeres.
Photo courtesy of Mary Lou Pardue and
Joseph G. Gall, Carnegie Institution.
7.5 Satellite DNAs Often Lie in
Heterochromatin
• Satellite DNA is often the major constituent of
centromeric heterochromatin.
• euchromatin – Regions that comprise most of the
genome in the interphase nucleus are less tightly coiled
than heterochromatin, and contain most of the active or
potentially active single-copy genes.
7.6 Arthropod Satellites Have Very Short
Identical Repeats
• The repeating units of arthropod satellite DNAs
are only a few nucleotides long.
– Most of the copies of the sequence are identical.
Figure 07.14: Satellite DNAs of D. virilis are related.
7.7 Mammalian Satellites Consist of
Hierarchical Repeats
• Mouse satellite DNA has evolved by duplication and
mutation of a short repeating unit to give a basic
repeating unit of 234 bp in which the original half-,
quarter-, and eighth-repeats can be recognized.
Figure 07.15: The repeating unit of mouse satellite DNA contains two half-repeats, which
are aligned to show the identities (in blue).
7.7 Mammalian Satellites Consist of
Hierarchical Repeats
Figure 07.16: The alignment of quarter-repeats identifies homologies between the first
and second half of each half-repeat.
7.7 Mammalian Satellites Consist of
Hierarchical Repeats
Figure 07.17: The alignment of eighth-repeats shows that each quarter-repeat consists of an
α and a β half.
7.7 Mammalian Satellites
Consist of Hierarchical
Repeats
Figure 07.18: The existence of an overall
consensus sequence is shown by writing the
satellite sequence as a 9 bp repeat.
7.8 Minisatellites Are Useful for Genetic
Mapping
• The variation between microsatellites or minisatellites
in individual genomes can be used to identify heredity
unequivocally by showing that 50% of the bands in an
individual are inherited from a particular parent.
• variable number tandem repeat (VNTR) – Very short
repeated sequences, including microsatellites and
minisatellites.
7.8 Minisatellites Are Useful for Genetic
Mapping
Figure 07.20: Alleles may differ by
number of repeats at a minisatellite
locus, so digestion generates restriction
fragments that differ in length.
7.8 Minisatellites Are Useful for Genetic
Mapping
• DNA fingerprinting – Analysis of the differences
between individuals of restriction fragments that
contain short repeated sequences, or by PCR.
– The lengths of the repeated regions are unique to
every individual, so the presence of a particular
subset in any two individuals shows their common
inheritance (e.g., a parent–child relationship).
7.8 Minisatellites Are Useful for Genetic
Mapping
Figure 07.21: Replication slippage occurs
when the daughter strand slips back one
repeating unit in pairing with the template
strand.