Chapter 4
Clusters
and
repeats
? Gene clusters are formed by duplication and divergence
? Sequence divergence is the basis for the evolutionary clock
? Pseudogenes are dead ends of evolution
? Unequal crossing-over rearranges gene clusters
? Genes for rRNA form tandem repeats
? ( The repeated genes for rRNA maintain constant sequence)
? Crossover fixation could maintain identical repeats
? Satellite DNAs often lie in heterochromatin
? Arthropod satellites have very short identical repeats
? Mammalian satellites consist of hierarchical repeats
? Minisatellites are useful for genetic mapping
Gene cluster is a group of adjacent genes that are identical or
related.
Gene family consists of a set of genes whose exons are related; the
members were derived by duplication and variation from some
ancestral gene.
Satellite DNA consists of many tandem repeats (identical or related)
of a short basic repeating unit.
Unequal crossing-over describes a recombination event in which
the two recombining sites lie at nonidentical locations in the two
parental DNA molecules.
4.1 Introduction
Figure 1.23
Chiasma
formation is
responsible
for generating
recombinants.
4.1
Introduction
Figure 1.24
Recombination
involves pairing
between
complementary
strands of the
two parental
duplex DNAs.
4.1
Introduction
Pseudogenes are inactive but stable components
of the genome derived by mutation of an
ancestral active gene.
假基因,类似于基因但不表达的 DNA序列。
不表现任何功能,是基因的退化形式。假基因在基因组中形成
稳定的和无活性的拷贝,由活化的原始基因突变而来,这是因
为存在着在某个阶段伤及基因表达的一种或多种缺陷(入启动
子错误、有缺陷的剪接信号、框架中有终止信号等)之故。一
旦不能产生正常的基因产物,就失去了对发生进一步突变的选
择性屏障作用,因此典型的假基因都有很多缺陷。某些假基因
有 3‘-多聚 A尾巴及准确地切掉了内含子,因而与 mRNA类似,
被认为是源自插入基因组的逆转录体(可能由某些病毒携带)。
4.2 Gene clusters are formed by
duplication and divergence
Figure 2.13 All functional globin genes have an
interrupted structure with three exons,The lengths
indicated in the figure apply to the mammalian b-
globin genes.
4.2 Gene clusters are formed by
duplication and divergence
Figure 4.1 Each of
the a-like and b-like
globin gene families
is organized into a
single cluster that
includes functional
genes and
pseudogenes.
4.2 Gene clusters
are formed by
duplication and
divergence
Figure 4.2 Clusters of b-globin genes and pseudogenes
are found in vertebrates,Seven mouse genes include 2
early embryonic,1 late embryonic,2 adult genes,and 2
pseudogenes,Rabbit and chick each have four genes.
4.2 Gene clusters are formed by duplication
and divergence
Figure 4.3 All globin
genes have evolved by
a series of duplications,
transpositions,and
mutations from a
single ancestral gene.
4.2 Gene
clusters are
formed by
duplication and
divergence
Figure 4.3 All globin
genes have evolved by
a series of duplications,
transpositions,and
mutations from a
single ancestral gene.
4.2 Gene
clusters are
formed by
duplication and
divergence
Divergence is the percent difference in
nucleotide sequence between two related DNA
sequences or in amino acid sequences between
two proteins.
Evolutionary clock is defined by the rate at
which mutations accumulate in a given gene.
Replacement sites in a gene are those at which
mutations alter the amino acid that is coded.
4.3 Sequence divergence is the basis
for the evolutionary clock
Figure 4.4
Divergence of DNA
sequences depends
on evolutionary
separation,Each
point on the graph
represents a pairwise
comparison.
4.3 Sequence
divergence is the
basis for the
evolutionary clock
Figure 4.5 Replacement
site divergences between
pairs of b-globin genes
allow the history of the
human cluster to be
reconstructed,This tree
accounts for the
separation of classes of
globin genes.
4.3 Sequence
divergence is the basis
for the evolutionary
clock
Processed pseudogene is an inactive
gene copy that lacks introns,contrasted
with the interrupted structure of the
active gene,Such genes presumably
originate by reverse transcription of
mRNA and insertion of a duplex copy
into the genome.
4.4 Pseudogenes are dead ends of evolution
Figure 16.19 Pseudogenes could arise by reverse
transcription of RNA to give duplex DNAs that become
integrated into the genome.
4.4 Pseudogenes are dead ends of evolution
Thalassemia is disease of red blood cells
resulting from lack of either a or b globin.
Unequal crossing-over describes a
recombination event in which the two
recombining sites lie at nonidentical
locations in the two parental DNA
molecules.
4.5 Unequal crossing-over
rearranges gene clusters
Figure 4.2 Clusters of b-globin genes and pseudogenes
are found in vertebrates,Seven mouse genes include 2
early embryonic,1 late embryonic,2 adult genes,and 2
pseudogenes,Rabbit and chick each have four genes.
4.5 Unequal crossing-over
rearranges gene clusters
Figure 4.6 Gene number can be
changed by unequal crossing-over,
If gene 1 of one chromosome
pairs with gene 2 of the other
chromosome,the other gene
copies are excluded from pairing,
as indicated by the extruded loops,
Recombination between the
mispaired genes produces one
chromosome with a single
(recombinant) copy of the gene
and one chromosome with three
copies of the gene (one from each
parent and one recombinant).
4.5 Unequal crossing-
over rearranges gene
clusters
Figure 4.7
Thalassemias
result from
various deletions
in the a-globin
gene cluster.
4.5 Unequal
crossing-over
rearranges
gene clusters
Figure 4.8
Deletions in the
b-globin gene
cluster cause
several types of
thalassemia.
4.5 Unequal
crossing-over
rearranges gene
clusters
Nontranscribed spacer is the region between
transcription units in a tandem gene cluster.
Nucleolar organizer is the region of a
chromosome carrying genes coding for
rRNA.
Nucleolus is a discrete region of the nucleus
created by the transcription of rRNA genes.
4.6 Genes for rRNA form tandem repeats
Figure 4.9 A tandem
gene cluster has an
alternation of
transcription unit
and nontranscribed
spacer and generates
a circular restriction
map.
4.6 Genes for
rRNA form
tandem repeats
Figure 4.10 The nucleolar
core identifies rDNA under
transcription,and the
surrounding granular cortex
consists of assembling
ribosomal subunits,This thin
section shows the nucleolus
of the newt Notopthalmus
viridescens,Photograph
kindly provided by Oscar
Miller.
4.6 Genes for rRNA
form tandem
repeats
Figure 4.11 Transcription of rDNA clusters generates a series
of matrices,each corresponding to one transcription unit and
separated from the next by the nontranscribed spacer,
Photograph kindly provided by Oscar Miller.
4.6 Genes for rRNA form tandem repeats
Figure 4.12 The nontranscribed spacer of X,laevis rDNA has an internally
repetitious structure that is responsible for its variation in length.
4.7 The repeated genes for rRNA maintain constant
sequence
Concerted evolution describes the ability of two related genes
to evolve together as though constituting a single locus.
Crossover fixation refers to 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).
Gene conversion is 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.
4.8 Crossover fixation could
maintain identical repeats
Figure 23.4 Group I introns have a
common secondary structure that
is formed by 9 base paired regions,
The sequences of regions P4 and
P7 are conserved,and identify the
individual sequence elements P,Q,
R,and S,P1 is created by pairing
between the end of the left exon
and the IGS of the intron; a region
between P7 and P9 pairs with the
3' end of the intron.
4.8 Crossover fixation
could maintain
identical repeats
Figure 23.4 Group I introns have a
common secondary structure that
is formed by 9 base paired regions,
The sequences of regions P4 and
P7 are conserved,and identify the
individual sequence elements P,Q,
R,and S,P1 is created by pairing
between the end of the left exon
and the IGS of the intron; a region
between P7 and P9 pairs with the
3' end of the intron.
4.8 Crossover fixation
could maintain
identical repeats
Figure 4.13 Unequal
recombination allows one
particular repeating unit to
occupy the entire cluster,
The numbers indicate the
length of the repeating unit
at each stage.
4.8 Crossover fixation
could maintain
identical repeats
Cryptic satellite is a satellite DNA sequence not
identified as such by a separate peak on a density
gradient; that is,it remains present in main-band DNA.
Euchromatin comprises all of the genome in the
interphase nucleus except for the heterochromatin.
Heterochromatin describes regions of the genome that
are permanently in a highly condensed condition,are
not transcribed,and are late-replicating,May be
constitutive or facultative.
4.9 Satellite DNAs often lie in heterochromatin
In situ hybridization is 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.
Satellite DNA consists of many tandem repeats (identical
or related) of a short basic repeating unit.
4.9 Satellite DNAs often lie in heterochromatin
Figure 4.14 Mouse
DNA is separated into
a main band and a
satellite by
centrifugation through
a density gradient of
CsCl.
4.9 Satellite DNAs
often lie in
heterochromatin
Figure 18.16
Individual bands
containing particular
genes can be
identified by in situ
hybridization.
4.9 Satellite DNAs
often lie in
heterochromatin
Figure 4.15
Cytological
hybridization shows
that mouse satellite
DNA is located at the
centromeres,
Photograph kindly
provided by Mary Lou
Pardue and Joe Gall.
4.9 Satellite
DNAs often lie in
heterochromatin
Figure 4.16 Satellite DNAs of D,virilis are related,
More than 95% of each satellite consists of a tandem
repetition of the predominant sequence.
4.10 Arthropod satellites have very short identical repeats
Figure 4.15 Cytological
hybridization shows that
mouse satellite DNA is
located at the
centromeres,Photograph
kindly provided by Mary
Lou Pardue and Joe Gall.
4.10 Arthropod
satellites have very
short identical repeats
Figure 4.17 The repeating unit of mouse satellite
DNA contains two half-repeats,which are
aligned to show the identities (in color).
4.11 Mammalian satellites consist of hierarchical
repeats
Figure 4.18 The alignment of quarter-repeats identifies
homologies between the first and second half of each
half-repeat,Positions that are the same in all 4 quarter-
repeats are shown in color; identities that extend only
through 3 quarter-repeats are indicated by grey letters in
the pink area.
4.11 Mammalian satellites consist of hierarchical repeats
Figure 4.19 The alignment of eighth-repeats shows that each quarter-repeat consists of
an a and a b half,The consensus sequence gives the most common base at each
position,The "ancestral" sequence shows a sequence very closely related to the
consensus sequence,which could have been the predecessor to the a and b units,(The
satellite sequence is continuous,so that for the purposes of deducing the consensus
sequence,we can treat it as a circular permutation,as indicated by joining the last
GAA triplet to the first 6 bp.)
4.11 Mammalian satellites consist of hierarchical repeats
Figure 4.20 The
existence of an
overall consensus
sequence is shown by
writing the satellite
sequence in terms of
a 9 bp repeat.
4.11 Mammalian
satellites consist of
hierarchical repeats
Figure 4.21 The
evolution of mouse
satellite DNA can be
explained by an
alternation of saltatory
replications and
accumulation of
mutations.
4.11 Mammalian
satellites consist of
hierarchical repeats
Figure 4.21 Digestion of
mouse satellite DNA with the
restriction enzyme EcoRII
identifies a series of repeating
units (1,2,3) that are
multimers of 234 bp and also
a minor series (?,1?,2?) that
includes half-repeats (see text
later),The band at the far left
is a fraction resistant to
digestion.
4.11 Mammalian
satellites consist of
hierarchical repeats
Figure 4.22 Alleles may
differ in the number of
repeats at a minisatellite
locus,so that cleavage
on either side generates
restriction fragments
that differ in length,By
using a minisatellite
with alleles that differ
between parents,the
pattern of inheritance
can be followed.
4.12 Minisatellites
are useful for
genetic mapping
Figure 4.22 Alleles may
differ in the number of
repeats at a minisatellite
locus,so that cleavage
on either side generates
restriction fragments
that differ in length,By
using a minisatellite
with alleles that differ
between parents,the
pattern of inheritance
can be followed.
4.12 Minisatellites
are useful for
genetic mapping
1,Almost all genes belong to families,defined by the possession of
related sequences in the exons of individual members.
2,An evolving set of genes may remain together in a cluster or may
be dispersed to new locations by chromosomal rearrangement.
3,Mutations accumulate more rapidly in silent sites than in
replacement sites (which affect the amino acid sequence).
4,A tandem cluster consists of many copies of a repeating unit that
includes the transcribed sequence(s) and a nontranscribed spacer(s).
5,Satellite DNA consists of very short sequences repeated many
times in tandem.
6,Unequal crossing-over appears to have been a major determinant
of satellite DNA organization.
4.13 Summary