STRUCTURAL ALTERATIONS IN CHROMOSOMES
Introduction
The
expression and inheritance of the sum total of characters of an organism is
determined by the number and sequence of genes of its cells. The changes in
architecture and morphology of chromosomes do not involve changes in the number
of chromosomes,but result from changes in the number or sequence of genes of
chromosomes.These changes are collectively known as chromosomal aberrations and were first analysed by Muller (1928) in
Drosophila and by Barbara McClintock
(1930) in Zea.Cytological
observations along with genetic studies have resulted in the identification of
following types of changes in the number or arrangement o genes:
A. Changes Involving Number
of Genes
i) Deletion or deficiency It signifies the loss or absence of a section of a
chromosome and may involve one or more genes.
ii) Duplication. It represents a gain in chromosomal material and in this case a part of
a chromosome is present in excess of the normal amount. Thus one or more genes
are present in more than two doses.
B Changes Involving Arrangement of Genes
i) Inversion. In this process a section of a chromosome gets inverted or rotates by
180° on its own axis. This changes the relative positions of genes on a
chromosome, but not their number.
ii) Translocation. It involves the transfer of a part of one chromosome to a nonhomologous
one, thereby changing the relative positions of genes but not their number.
All
types of chromosomal aberrations are caused by a break in the chromosome or its
chromatid. When broken ends rejoin to restore the original chromosome structure
and gene sequence, there is no change and restitution occurs. Aberrations occur
when broken ends are lost or get joined to a wrong chromosome or in a wrong
order. The number of breaks, their location, and the pattern in which broken
ends get joined determines the type of chromosomal aberration. Their study is
important because they occur in nature quite frequently and have been
instrumental in the evolution of many species of plants and animals. Their
frequency can be increased with the help of ionizing radiations or certain
chemical agents.
Deletion or Deficiency
If a section of chromosome gets broken and
detached, some genes are lost from the chromosome. Acentric fragments are
either digested by nucleases or fail to move to either of the poles during cell
division. Usually they get excluded from the daughter cells. Sometimes they
move towards one end of the cell, just by chance, and get included in one of
the two daughter cells. In either case a population of cells arises which is
deficient for a few genes. If gametes arise from deficient cells, deletion is
transmitted to the next generation.
Deletion
can be terminal i.e. a terminal section of chromosome is absent, or intercalary
i.e. an intermediate section or portion of chromosome is lost. Only one break
is necessary for terminal deletion, whereas for intercalary deletion two breaks
(one on either end of the deleted region) are essential. A break for
intercalary deletion results into three pieces of chromosome, the middle one of
which is lost and the other two get joined again. Broken acentric fragments of
chromosomes, which are in the process of being digested, sometimes appear as small
chromatin bodies in cells and are known as micronuclei.
Experimental
proof for deletion was obtained by Bridges (1916-1919) who studied the
inheritance pattern of sex linked lethal characters which had arisen
spontaneously in a population of fruit-flies.
Deletion
can be recognized by distortions of chromosomes during meiosis pairing of
homologous chromosomes or during somatic pairing in specialized tissues like
salivary glands of Drosophila. Due to a terminal deletion one of the paired
chromosomes appears to be much longer than the other. This can be seen during
pachytene in maize and in salivary gland chromosomes of Drosophila. Due to an
intercalary deletion the normal chromosome forms a loop near the deficient
region of its homologous, because only identical regions pair with each
other.Inheritance patterns of genes of deleted regions and cytological studies
of pairing between normal and deleted chromosomes have helped a lot in finding
out the relative positions of genes on chromosomes. Thus, deletions have helped
in constructing and verifying linkage maps of a variety of organisms like
maize, Drosophila, bacteriophages etc.
Duplication
The
presence of a part of a chromosome in excess of the normal complement is known
as duplication. A broken section of a chromosome attaches itself to a normal
homologous or non homologous chromosome or in the presence of a centromere
behaves like an independent chromosome and gets included in an otherwise normal
nucleus. Consequently some genes are present in a cell in more than two doses.
Depending on the mode of joining of the duplicated region to a chromosome or
its independent existence, duplications can be of the following types:
1) Extra-chromosomal
duplication. In the presence of a centromere the duplicated part of a
chromosome may behave as an independent chromosome.
2) Tandem
duplicated. In this case the duplicated region situated just by the side of
the normal corresponding section of the chromosome and the sequences of genes
are the same in the normal and duplicated regions.
For example, if the sequence of genes in a
chromosome is ABC.DEFGH (full stop represents the centromere) and if the
section containing the genes DEF is duplicated, the sequence of genes in tandem
duplication will be ABC.DEFDEFGH.
3) Reverse
tandem duplication. In this case the sequence of genes in the duplicated
section of a chromosome is just the reverse of a normal sequence. In the above
example, therefore, the sequence of genes as a result of reverse tandem duplication
will be ABC.DEFFEDGH.
4) Displaced
duplication. In this case the duplicated section is not adjacent to the
normal section Depending on whether the duplicated portion is on the same side
of the centromere as the original section or on the other side; displaced duplication
can be homobrachial or heterobrachial:
homobrachial
duplication = ABC.DEFGDEFH.
heterobrachial duplication = ADEFBC.DEFGH.
5) Transposed
duplication. In this case the duplicated section is attached to a non
homologous chromosome. If ABC.DEFGH and LMNOPQ.RST represent the genes
sequences of two non homologous chromosomes, a transposed duplication will
result into chromosomes with gene sequences ABC.DEFGH and LMNDEFOPQ.RST. The
duplicated region can be transposed to a non homologous chromosome interstitially
or terminally.
Duplications
involving various regions of the X chromosome in Drosophila have been studied
in detail. Flies heterozygous for the Bar (B) gene have rod shaped or
rectangular eyes instead of normal round eyes. Flies homozygous for this gene
have very small eyes. In 1936 Muller and Bridges found independently of each
other that bar eyes are caused due to a duplication of the region of the X
chromosome. A reduplication of this region results into Ultrabar or doublebar
or very small eyes.
Duplications
and reduplications of the Bar region can be very easily seen in the salivary
gland chromosomes. As the number of Bar genes increases, the eyes become
smaller. Duplications, reduplications and deletions may arise due to unequal cross-overs.
Like
deletions duplications also result into unequal or looped out configurations at
the time of pairing of homologous chromosomes. Crossing –over in reverse tandem
duplication results into a dicentric chromosome. This can frequently seen in chromosomes
of maize. Irrespective of whether sister or non-sister chromatids are involved
in a cross-over, dicentric chromosomes are produced. As the two centromeres
move towards two different poles, a chromosome “bridge” is formed which later
on breaks at any point along the bridge. The broken ends become “sticky” and a
replication of the chromosome produces two sister chromatids which are joined
together due to their sticky ends. Therefore, the bridge-breakage-fusion cycle
goes on indefinitely. In sporophytic tissues of plants however, sticky ends are
not found.
Duplication
has played a great role in evolution. It is a means of increasing the number of
genes in a cell so that different copies of the same gene may change in
different directions without disturbing the normal functions of an organism. It
has been suggested that all cases in which different gene pairs affect the same
character (e.g. multiple factors, complementary genes, etc.) arose initially as
duplications of single genes .More evolved organisms have been found to have
more repetitions of DNA sequences.
Inversion
Inversion involves a rotation of a part of a
chromosome or a set of genes by 180° on its own axis. Breakage and reunion is
essential for inversion to occur and the net result is neither a gain or loss
in the genetic material but simple a rearrangement of the gene sequence.
Inversion that include the centromere are known as pericentric (around the
centromere), whereas those which do not involve the centromere are known as
paracentric ones.
If the normal sequence of gene in a chromosome is
ABC.DEFG, the sequence in paracentric and pericentric inversions will be
ABC.DGFE and AED.CBFG, respectively. In organisms which are homozygous for
inversions, zygotene and pachytene is normal because of similarity of
abnormalities in the homologous chromosomes. But heterozygous inversions result
into looped configurations during pachytene. If the heterozygous inversion is
small enough, the opposing inverted regions fail to pair and crossing-over is
suppressed in this part of the chromosome. A crossing-over in the inverted
region of a heterozygous paracentric inversion results into a chromosome with
two centromeres and an acentric fragment. As the two centromere of the
dicentric chromosome move towards two opposite poles, a chromatid bridge is
formed at anaphase I. The acentric
fragment is not attached to the spindle, lies free in the cytoplasm and is not
disjuncted properly. Thus meiotic separations are usually abnormal.
In case meiotic separation is normal, four types of
gametes are formed – one with a normal gene sequence, second with an inverted
gene sequence, third with a dicentric chromosome and duplication of some genes,
and fourth with an acentric chromosome and deletion of some genes. The latter
two types of gametes are usually not viable, with the result that heterozygotes
for paracentric inversions are highly sterile and only parent-like progeny are
produced. In other words, crossing-over is apparently suppressed due to paracentric inversion.
Dicentric bridge formed in maize female tissue as a result of such
crossing-over results into a bridge-breakage-fusion cycle. Pollen grains show a
high degree of sterility. Multiple cross-overs reduced the suppression effect,
especially with respect to those genes between which two (or even number of)
cross-overs occur, because their result is the same as no cross-over (only if
the same two strands are involved in even number of exchanges).
Crossing-over in a heterozygous pericentric
inversion does not result into a chromatid bridge, but results into deletions
and duplications in the gametes. Therefore, pericentric inversions also
apparently suppress crossing-over. Although heterozygotes for pericentric inversions
produce a significant proportion of invaible gametes and unbalanced zygotes as
a rule, Drosophila is an exception because in the females there is reduced
paring and consequent reduced crossing-over in the inverted region between the
homologous chromosomes. Pericentric inversions involving unequal arms result
into drastic changes in the morphology of chromosomes. For example, metacentric
(V-shaped) chromosomes can be transformed into acentric (rod-shaped) ones or vice-versa.
Fertility of inversion of
homozygote and sterility of inversion heterozygote leads to the establishment
of two groups which are mutually fertile but do not breed well with the rest of
species. Thus, two varieties are established which evolve in different
directions and later become reproductively isolated species. There is plenty of
cytological evidence to prove that such evolutionary mechanisms have and are
operating in Drosophila and a number of other organisms.
Inversion has been useful in
establishing and maintaining a heterozygous condition, because in inversion
heterozygotes crossing-over is suppressed and only parental progeny are
produced. Recessive lethals can be added advantage because heterozygotes for
them will be viable but homozygote nonviable. Quite a few strains of Drosophila are routinely maintained with
the help of lethal genes and inversion heterozygosity.
Translocation
Translocation involves the transfer of a part of a
chromosome or a set of genes to a non-homologous chromosome. It results into a
change in the sequence and position of the genes but not their quantity, means
changes involving arrangement of genes.
An important type of translocation having
evolutionary significance is known as reciprocal translocation or segmental
interchanges which involve mutual exchange of chromosome segments between two
pairs of non-homologous chromosomes.
Translocation heterozygotes
When translocation is present in only one chromosome
this will be a translocation heterozygote and when translocation is present in
both non-homologous chromosome then this will be a translocation homozygote. In
translocation homozygote there is no problem during meiotic pairing but in case
of Translocation heterozygotes, due
to pairing between homologous segments of chromosomes, a cross shaped figure
involving 4 chromosomes will be observed at pachytene sub-stage of meiosis
I.These 4 chromosomes at metaphase I can have one of the three orientations –
1. Alternate – In this
orientation alternate chromosome (I and III) will be oriented toward the same
pole.
2. Adjacent I – In this
orientation adjacent chromosome (side by side) having non-homologous centromere
will orient towards the same pole.
3. Adjacent II – In this
orientation adjacent chromosome (I and III) having homologous centromeres will
orient towards the same pole.
Irrespective of whether
segregation during meiosis I is alternate or adjacent, 2 types of gametes will
be produced. Alternate segregation will produce balanced gametes but adjacent
segregation will produced gametes which will be duplicated for some genes or
deficient for few others, such unbalanced gametes will not be viable. This is
the reason why organisms with heterozygous translocation are semi sterile. Such
instance are very common in wheat, maize, pea, datura etc.In plants like Rhoeo and Oenothera, translocation heterozygote have become stable due to the
presence of balanced lethals or lethals that are not expressed under
heterozygous conditions.
Translocations have been
found in human beings also. They can be detected by karyotype analysis.
Reciprocal translocation between chromosome 5 and 18 are well documented.
Sometimes reciprocal translocation results into heteromorphic autosomal pairing
involving chromosomes 13, 14, 15, 16, 17 or 18 and chromosome 21 (the trisomy
of which results into Down syndrome). One of the autosomes of such a pair is
normal whereas the other one has an extra piece, corresponding to the long arm
of chromosome 21; in addition to the normal pair of chromosome 21.Such
individuals are virtually trisomic for chromosome 21 and therefore show Down’s
syndrome. They arises of a female with reciprocal translocation between
chromosome 15 and 21 marries a normal male.
Translocations results into changed linkage
relationships between genes because non linkage groups are established.
Independently assorting genes become linked and linked genes began to show
independent assortment provided their linkage groups are changed because of
translocation.
Chromosomal translocation result into change in the
sequence of gene but not their number, very frequently result into a change in
phenotype of the organism. This clearly shows that the expression of some genes
is affected by their position on a chromosome. This effect is known as position effect.
Breeding behaviour of translocation
heterozygotes
Presence of
translocation heterozygosity can be detected by presence of semisterlity and
low seed set. This can then be confirmed at meiosis by quadrivalent (4
univalent) formation. As shown in figure only two types of functional gametes
are formed which results from alternate orientation. The functional gametes
will give rise three kinds of progeny namely –
1. Normal,
2. Translocation heterozygote,
3. Translocation homozygote.
These three types would be
obtained in 1:2:1 ratio.
Complex translocation heterozygotes
Complex translocation can be obtained by recurrent
irradiation or by intercrossing simpler translocation stocks to yield complex one.
Both these methods were used successfully. In both cases where complex rings
could be synthesized, high sterility was associated with the ring, which became
a major barrier in utilization of these rings in Oenothera. Genus Oenothera was studied 1920 – 1930 and cytogenetics
structure leading to evolution in this genus was examined. In this genus 2n =
14 and all 7 chromosomes of a haploid complement have median centromere.
In O.
Lamarkiana a ring of only 12 chromosomes instead of ring of 14 chromosomes is
obsereved and 2 chromosomes forming a bivalent is seen. In this genus
Oenothera, few permanent and few temporary translocations are found which
develops into different species like O.
biennis, O.strigosa and O.irrigua, O.hookeri.
These species differ in phenotypes like flower size
etc and can be identified.
Translocation Tester Sets
In many chromosomes of a particular species may lack
any type of markers which could otherwise enable identification of individual
chromosomes. Genetic and environmental variations in chromosomal phenotype make
it difficult for identification of individual chromosome. Tester sets
(Translocation homologous with known chromosomes involved in translocation) is
used to identify such chromosomes, because individual chromosome involved in a
structural change (Translocation) or in anenploidy can then be identified by
making crosses to the tester set. The significance of such a tester set can be
understood in identification of unknown translocation, trisomics and monosomics.
For the synthesis of translocation tester set seeds
were irradiated and grown M1 population. Then the plants of M1
population selected were partial pollen sterility is found and meiotic
behaviour of these selected plants were studied to confirm translocation
heterozygotes (a ring of 4 chromosomes is seen). Then selfing is done between
such translocated heterozygotes, as self pollination crates translocation
homozygosity, and harvest the seed of individual plants separately. Then grow
single plant progenies and select each progeny for plants with only bivalents
(as bivalent showing translocation homozygote). This generation is M2
generation. M2 generation plants were crossed with normal plants and
study the meiotic behaviour of these crossing result or F1 hybrids.
Identify chromosome involved in translocation. Such translocation tester sets
are identified in maize, barley, pea, rye and tomato.
Robertsonia Translocation
Robertsonia
translocation was first discovered by W.R.B Robertson in 1911.
It is also known as centric fusion translocation.
Chromosomal breakage of acrocentric chromosomes near the centromeres results
into robertsonia translocation.
This chromosomal breakage results into 2 segments,
one large segment and another small segment. The larger segments fuse together
to form a new submetacentric or metacentric character. While smaller segments
may fuse to form new character or may be lost but in both case they are of no
use as smaller part of acrocentric character contain many non essential
heterochromatic DNA.
Person with balanced robertsonia translocation will
have 45 chromosomes only.
The human chromosomes of D and G groups shows this
translocation i.e. chromosome no. 13, 14, 15 and 21 and 22.
Eg: Although translocations generally have been of
greater importance in the plant kingdom than in the animal kingdom, one type of
translocation has had some evolutionary significance in animals. This
aberration, described as a centric fusion, is actually a translocation between
two chromosomes. It has been found in Drosophila, arthropods, certain birds,
and mammals. Studies with Drosophila have indicated that translocations,
particularly centric fusions, have caused evolutionary changes of chromosome
numbers in various species. Their principal effect has been to reduce the chromosome
numbers. Example of centric fusions are given, which presents the possible
evolutionary patterns in two subgenera, Drosophila
and Sophophora. Each fusion involves
a translocation of almost the entire arm of a rod chromosome to produce a
V-shaped chromosome. Translocations of small portions of an arm are rare in Dorsophila. There are other differences
besides the translocations in the chromosomes of the species represented,
including inversions, and the genetics of these organisms is rather complex,
especially since hybridization is possible among many of the species.
A similar reduction in chromosome number is
exhibited by the plant Crepis. The
more primitive species of Crepis have
a basic chromosome number of six (n = 6), whereas the more advanced species
have basic number of three, four, and five. Reciprocal translocations have
contributed greatly to this evolutionary trend toward reduction in chromosome
number. In those cases where centric fusions lead to a decrease in chromosome
number, little genetic material is lost from the genome, since most of the
translocated chromosome is retained. Thus there is little loss in viability or
fertility of the offspring of later generations.
B-A Translocation
In 1947, Roman reported a special type of
translocation in maize involving translocation between two normal chromosomes A
and B, in these chromosomes breakage and reunion takes place. Chromosome A
breaks at one point and same thing in B chromosome, a breakage takes place.
Both the broken pieces reunite as A with a piece of B chromosome and B with a
piece of A chromosome. This translocation takes place only in one chromosome
i.e. it takes place in heterozygotic condition. At metaphase plate a
quadrivalent is found having A, AB, B and BA.
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