Download Chapter 6

Chapter 6
Clusters and Repeats
6.1
Introduction
 A gene family consists of related genes that
arose by duplication and variation from a single
ancestral gene.
6.2
Gene Duplication Is a Major Force in
Evolution
 Duplicated genes may
diverge to generate
different genes or one copy
may become an inactive
pseudogene.
Figure 6.04: Duplicated genes may diverge
or be silenced.
6.3 Globin Clusters Are Formed by Duplication
and Divergence
• All globin genes are descended by duplication
and mutation from an ancestral gene that had
three exons.
• The ancestral gene gave rise to myoglobin,
leghemoglobin, and α and  globins.
6.3 Globin Clusters Are
Formed by Duplication and
Divergence
Figure 6.08: Globin genes have duplicated and
diverged.
6.3
Globin Clusters Are Formed by
Duplication and Divergence
• The α- and -globin genes separated in the
period of early vertebrate evolution.
– After, duplications generated the individual clusters of
separate α- and -like genes.
• Once a gene has been inactivated by mutation,
it may accumulate further mutations and become
a pseudogene.
– It is homologous to the active gene(s) but has no
functional role.
6.3
Globin Clusters Are Formed by
Duplication and Divergence
Figure 6.05: Globin genes are organized in two clusters.
6.4
Sequence Divergence Is the Basis for the
Molecular Clock
• The sequences of orthologous genes in different
species vary at:
– replacement sites (where mutations have caused
amino acid substitutions)
– silent sites (where mutation has not affected the
amino acid sequence)
• Silent substitutions accumulate ~10× faster than
replacement substitutions.
6.4
Sequence Divergence Is the Basis for the
Molecular Clock
• The evolutionary divergence between two DNA
sequences is measured by the corrected
percent of positions at which the corresponding
nucleotides differ.
• Mutations may accumulate at a more or less
constant rate after genes separate
– The divergence between any pair of globin
sequences is proportional to the time since they
shared common ancestry.
6.4
Sequence Divergence Is the Basis for the
Molecular Clock
Figure 6.09: Silent substitutions occur more often than replacement
substitutions.
6.5 The Rate of Neutral Substitution Can Be
Measured from Divergence of Repeated
Sequences
 The rate of substitution per year at neutral sites
is greater in the mouse than in the human
genome.
6.6
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.
6.6
Unequal Crossing Over Rearranges Gene
Clusters
Figure 6.12: Unequal crossing-over creates a duplication and a deletion.
6.6 Unequal Crossing Over Rearranges
Gene Clusters
• Different thalassemias are caused by various
deletions that eliminate α- or -globin genes.
– The severity of the disease depends on the individual
deletion.
6.6
Unequal Crossing Over Rearranges Gene
Clusters
Figure 6.13: α-Thalassemias are caused
by deletions.
Figure 6.14: β-Thalassemias are
caused by deletions.
6.7 Genes for rRNA Form Tandem Repeats
Including an Invariant Transcription Unit
• Ribosomal RNA is coded 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.
6.7 Genes for rRNA Form Tandem Repeats
Including an Invariant Transcription Unit
• The genes in an rDNA cluster all have an
identical sequence.
• The nontranscribed spacers consist of
shorter repeating units whose number varies
so that the lengths of individual spacers are
different.
Figure 6.18: The rDNA promoter has repetitious regions.
6.8
Crossover Fixation Could Maintain
Identical Repeats
• Not all duplicated copies of genes are become
pseudogenes.
• Unequal crossing over changes the size of a
cluster of tandem repeats.
• Individual repeating units can be eliminated or
can spread through the cluster.
6.9
Satellite DNAs Often Lie in
Heterochromatin
• Highly repetitive DNA has a very short repeating
sequence and no coding function.
• It occurs in large blocks that can have distinct
physical properties.
• It is often the major constituent of centromeric
heterochromatin.
Figure 6.20: Mouse satellite DNA forms a distinct band.
6.10 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 6.22: D. virilis has four
related satellites.
6.11 Mammalian Satellites Consist of
Hierarchical Repeats
 Mouse satellite DNA has evolved by duplication
and mutation of a short repeating unit.
 This gives a basic repeating unit of 234 bp in which
the original half, quarter, and eighth repeats can be
recognized.
6.11 Mammalian Satellites
Consist of Hierarchical Repeats
Figure 6.26: The mouse satellite DNA consensus is 9 bp.
6.12 Minisatellites Are Useful for Genetic
Mapping
 The variation between microsatellites or
minisatellites in individual genomes can be used
to identify heredity unequivocally
 Done by showing that 50% of the bands in an
individual are derived from a particular parent.
6.12 Minisatellites Are Useful for Genetic
Mapping
Figure 6.28: Minisatellite number differs between individual genomes.
Figure 6.29: Replication slippage changes repeat length.