Changes in Number and Arrangement of Genes

In this article we will discuss about the changes in number and arrangement of genes.

Changes in the Number of Genes:

(i) Deletion and Deficiency:

A single chromosome may result in a loss of small piece at the terminal end is said as terminal deficiency or deficiency. Sometimes a chromosome may break, however, at any two points, releasing an intercalary segment which may result ring or rod shaped, if its broken ends are fused.

If a centromere is present in the broken segment, it survives as a small but deficient chromosome. If there is no centromere with the broken segment, it is said to be deletion and is soon lost during the nuclear division.

A chromosome which shows deletion, becomes a deficient chromosome. In the case of diffuse centromere, the deleted segment of the chromosome retains its survivality and is added as an extra-chromosome to the original set.

In this type of structural change, the total gene content of the organism is affected. If ABCDEFG are the genes in a chromosome, then ABCDE is deficiency and ABFG is deletion. According to Roberts (1975) all deficiencies are really interstitial or deletion because of universal presence of telomere.

Cytological effect of deletion:

In the deletion heterozygote, pairing of chromosomes takes place normally but in the region of the deletion where a number of genes are missing, the normal chromosomes is pushed out in the form of a loop and this is generally referred to as buckle formation. Deficiency reduces the amount of crossing-over.

Genotypic and phenotypic effects of deficiencies:

Deficiency is lethal due to loss of genes. Individuals with homozygous deficiency fail to survive because a complete set of genes is absent. When a segment is lost from only one member of a homologous pair, forming a deficiency heterozygote, the individual survives but shows abnormal or unusual phenotypic effect.

The loss of very small segment of a chromosome by deletion behaves like a Mendelian unit in inheritance. Therefore, very small deficiencies are some times mistaken for gene mutation.

In other words, small deletions might not prevent the development of the organism, but they produce some mutant character in the individual. A classical case of deficiency was discovered and worked out by Bridges in 1917.

A mutant character in Drosophila called notch produces a notched margin of the wings. This is due to a small deletion in a certain part of the X-chromosome. It inherited as sex-linked dominant in the female and lethal in the male.

In the F₁ offsprings the females with notched wings were all white eyed, while the normal expectation would be red eyed forms, since red is a dominant character. In the absence of a dominant allele due to deletion, the recessive gene finds expression phenotypically. This kind of unexpected expression of a recessive character which is caused by the absence of a dominant allele is called psendodominance.

(Deletion may be terminal in which missing segments are at the end of chromosome and they may be intercalary in which missing parts are in the middle of the chromosome.)

(ii) Duplication:

The presence of a part of a chromosome in excess of the normal complement is known as a duplication or sometimes a segment or a part of the chromosome becomes repeated in the same chromosome. These additional duplicated segments are called duplications.

Occasionally a nucleus is found to be aberrant in that it has extra material beyond that found in the normal chromosomal complement. The extra material may be either in the form of whole chromosomes or extra sets of chromosomes (if the broken piece has a centromere, it is included as an extra chromosome) or it may be just a part of the chromosome.

The last one is referred to as duplication which is different from the first two. That is, addition of one or more genes as a result of which the organism carries the same segment of the chromosome repeated in its haploid chromosome complement.

(Under deletion and deficiency loss of one or more genes is exhibited. In duplication addition of one or more genes, as a result of which the organism carries the same gene repeated in its haploid chromosome complement).

Kinds of Duplications:

(a) Extra-chromosomal Duplication:

If a centromere is present in the broken out piece, it behaves like an independent additional or extra chromosome.

(b) Tandem duplication:

The duplicated segment lies by the side of the same genes, in the chromosome. The duplicated genes lie in the same order as in the normal chromosome e.g., if the order of genes in the normal chromosome is ABCDEFGH.IJKL the tandem duplication shall be ABCDECDEFGH.IJKL (full stop represents the centromere).

(c) Reverse tandem Duplication:

In this case the order of the genes in the duplicated segment of a chromosome is just the reverse of the original sequence. For example, in the above case, it would be ABCDEEDCFGH.IJKL.

(d) Displaced Duplication:

In some cases the duplicated segment does not lie adjacent or near to the normal segment. Depending on, whether the duplicated portion, is on the same side of the centromere (homo-brachial) or on the other side as the original (heterobrachial). In this case we would have ABCDEFGCDEH.IJKL.

(e) Translocation or Transposed duplication:

In this case the duplicate segment is attached to a non-homologous chromosome. The duplicated region can be transposed to a non-homologous chromosome interstitially (or intercalary) or terminally (terminal). In this case, it would be MNOPCDEQ.RSTUV.

In Drosophila Bridges found that some individuals which are definitely homozygous for recessive genes were found to exhibit the dominant characters. This on analysis, has been found due to extra chromosomal material carrying the dominant gene.

If the extra chromosomal material is provided with a centromere it might exist as a separate chromosome, but when it is without a centromere, it is attached to one of the normal chromosome. Duplications are less harmful than those of the effects of deletions.

A small segment of a chromosome might some times be duplicated as a result of unequal crossing over and such a duplication is referred to as repeat. In Drosophila mutant bar eyes which are narrow and constricted are due to small duplicated gene. Duplication has helped in evolution. Due to increase in number of genes, it is possible for different mutations to appear in the same gene without affecting the normal functions of the organism.

Changes in the Arrangement of Gene Loci:

(i) Translocation:

The term translocation was used by Bridges and Morgan in 1923 to indicate the unusual behaviour of chromosomes during which a segment from one of them becomes attached to another chromosome. This is the important and the most complex of all the chromosomal aberrations. During this process, a deleted segment moves from its normal position in one chromosome to a new situation in a different chromosome.

In translocation, segments of equal or unequal lengths are exchanged between two members of a homologous pair, or between non-homologous chromosomes. This exchange between chromosomes is called a mutual or reciprocal translocation.

In simple translocation only a piece of chromosome becomes attached to other chromosome without exchange. It is, however, suspected that simple translocation is also reciprocal but one of the segments is very small.

Besides simple and reciprocal translocations one more type of translocation is visible which involves breakage at three points but union at two points known as Shift translocation. Furthermore in allelosomal translocation interchange of segments occur between non-homologous chromosomes.

Translocations do not involve any loss or addition of chromosomal parts but simply rearrangement of its parts or genes in the chromosomes, not the quality or quantity of the genes.

For this reason, they are some times referred to as chromosomal rearrangements. They reduce the crossing-over by hindering chromosome pairing. Individuals carrying the rearrangements are phenotypically normal unless the relations of a gene or genes to adjascent genes, affect the phenotypic expression i.e., “position effect.”

Another rare type of “lateral translocation” has also been observed, in which a trans-located segment becomes attached to the sides of the receiving chromosome.

Translocation was referred to as “illegitimate” crossing-over in the beginning, indicating the two processes, resemble each other. The chief similarity between the both is as (i) there is breakage of chromosomes followed by union and exchange of segments.

But translocation and crossing-over differ from each other in the following respects or points:

(i) Crossing-over occurs as a natural and normal process during which segments of non-sister chromatids of equal size are exchanged between homologous chromosomes. The non-sister chromatids show breakage at corresponding points and new combination of genes are formed but no new gene is introduced. The percentage of crossing over may also be predicted in most cases.

(ii) In a typical translocation there is an exchange of non-homologous chromosomes. Thus genes from outside are introduced into the linkage group. Translocations are never under prediction and do not follow any set rule. It is not necessary that the exchanged segments may be of equal size.

Cytological effect of translocation:

The genetic techniques for detecting and studying translocations will be more easily understood when the cytological phenomena produced by translocations are known. Suppose that two chromosomes having respectively the genes ABCDE.FGHI and LMNOPQ.RST exchange segments and give rise to translocation chromosome LMNDE.FGHI and ABCOPQ.RST.

The individual thus formed receives from one of its parents the normal and from the other parent the translocation chromosomes. Such an individual is a translocation heterozygote. Since the chromosome pairing (synapsis) at the Meiotic prophase I, zygotene, is caused by specific attraction of homologous segments containing allelic genes, a translocation heterozygote may be expected to produce a cross shaped pairing.

Occurrence of crossing over in each of the four arms of the cross will result in formation of chiasmata in each arm. Instead of bivalents i.e., a pair of synapsed homologous chromosomes there will be formed a quadrivalent.

A group of four associated chromosomes, each member of the group being partially homologous to two other chromosomes in the group. The quadrivalent will appear at diakinesis and at metaphase I of the first meiotic division as a circle or ring of four chromosomes, which may be either twisted as shown in figure, left, or open as in the centre drawing of the same figure.

If chiasmata fail to be formed in one arm of the pachytene or diplotene cross, the ring is transformed into an open chain of four chromosomes. Such rings or chains of chromosome were observed and interpreted by Belling at Meiosis in the Datura and were thereafter found in maize, peas, wheat, Tradescantia and other plants and in some animals. They occur regularly in many evening primroses plant which bear yellow flowers.

There are different ways in which the chromosomes associated in a ring or chain may be distributed to the gametes formed as a result of meiosis. The two original chromosomes, ABCDE.FGHI and LMNOPQ.RST may go to the same gamete, and the translocation chromosome, ABCOPQ.RST and LMNDE.FGHI, to another gamete.

It may be noted that in each of these gametes, every gene symbolized by a letter occurs once only, as gametes are formed by normal individuals. On other hand, if chromosomes adjascent in the ring go to the same pole at the meiotic division, the four kinds of gametes are formed.

The common property of these four kinds of gametes is that they carry certain genes twice and do not have some genes at all. In other words, they carry duplications for some and deficiencies for other genes.

Translocations result into changed linkage relationships between genes. New linkage groups are established. Independently assorting genes becomes linked and linked genes begin to show independent assortment, provided their linkage groups are changed because of translocation.

[Heterozygous translocations are semi-sterile. In animals, some times, the unbalanced gametes are visible but the zygotes formed by them are not able to undergo normal development and differentiation. In plants like Rhoeo and Oenothera translocation heterozygotes have become stable due to the presence of balanced lethals or lethals that are not expressed under heterozygous conditions],

(ii) Inversion:

There are translocations occurring within single chromosome. It was primarily demonstrated by Sturtevant and Dobzhansky in the salivary gland chromosome of Drosophila.

Inversion involves a rotation of a part of a chromosome or a sets of genes by 180° on its own axis. Breakage and reunion is essential for reversion to occur and the net result is neither a gain nor a loss in the genetic material but simply a rearrangement of the gene sequence. They may be either terminal (occurrence at the end of chromosome) or intercalary when changes occur in the middle of chromosome.

Inversions that include the centromere are known as pericentric inversions where as those which do not involve the centromere are known as paracentric ones. If the normal order of genes in a chromosome is ABC.DEFG the sequence or order in paracentric and pericentric inversions will be ABC.DGFE and AED.CBFG respectively.

In individuals which are homozygous for inversions, zygotene and pachytene is normal because of similarities of abnormalities in the homologous chromosomes. But heterozygous inversion is small enough, the opposing inverted regions fail to pair and crossing-over is prevented in this part of the chromosome.

A crossing-over in the inverted region of heterozygous paracentric inversion results in to a chromosome with two centromeres and an acentric segment. As the two centromeres of dicentric chromosome move towards two opposite poles, a chromatid bridge is formed at anaphase I. The acentric segment is not attached to the spindle, lies free in the cytoplasm and is not free 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 later two types of gametes are usually not viable with the result that heterozygotes for paracentric inversions are highly sterile and only parent like a progeny are produced.

In other words, crossing-over is prevented due to a paracentric inversion. Crossing-over in a heterozygous pericentric inversion does not result into a chromatid bridge, but results in to deletions and duplications in the gametes. Therefore, pericentric inversions also apparently prevent crossing over.

Pericentric inversions involving unequal arms result in to drastic changes in the morphology of chromosomes. For example, metacentric (V-shaped) chromosomes can be transformed in to rod shaped (acrocentric) ones or vice-versa.

As inversion homozygotes are fertile and inversion heterozygotes are sterile, leads to the establishment of two groups of organisms within same species.

Thus, inversion has been useful in maintaining a heterozygous condition, thus useful in the origin of new species. In inversion, crossing over is suppressed and only parental progenies are produced. Recessive lethals can be of added advantage because heterozygotes for them will be viable but homozygous non viable.

Position effect:

The various chromosomal rearrangements described above often causes visible changes in the organisms. These visible phenotypic changes produced as a result of change in chromosomal segments constitute position effects.

This changed behaviour of genes due to rearrangement has been studied in Drosophila and first discovered by Sturtevant and Bridges in 1925. They found that the formation of Bar eye in Drosophila is due to position effect.

Lewis has classified position effects into two categories:

(i) Variegated type

(ii) Stable type

(i) Variegated type:

This type of position effects have been studied by Muller and others. These effect result in somatic instability of gene action. Variegated position effects result in the diversification of a character usually seen in a particular structure or area of the body specks of different colours, for e.g., may occur in the eyes of Drosophila following rearrangement of the ‘w’ (white eye) locus.

Inversions or translocations that place ‘w’ near the heterochromatin may cause white variegation or mosaicism for eye colour. This concept of heterochomatinisation producing variegated position effects hold goods in various eye colour examples.

(ii) Stable type:

A large number of structural rearrangement in Drosophila produce somatic stable position effects. These include barred eye, hairy wings etc. The classical examples of bar eye was done by Sturtevant and Bridges. In this bar character, eyes become narrow and number of facets have reduced. This arise as a result of duplication of genes.

There is an approximate quantitative relation between number of chromosome segment and the size of the eye. When segment was duplicated in various ways the barred character became prominent with the reduction in facets producing barred, double barred and ultra barred eyes. Two hypothesis have been put forward to explain the mechanism of position effect.

1. Kinetic hypothesis:

This theory assumes that position effects are caused as a result of local interaction between the gene products of adjascent loci or is based on the change in the chemical environment in which the gene is placed after the rearrangement. It implies that single gene is not completely independent in producing the position effects but action is influenced by the neighbouring genes.

2. Structural hypothesis:

According to this view, there is produced a sort of physical change in the gene locus itself where break occurs, nucleoprotein molecules may be deformed during the physical change.

Non-Disjunction of Chromosomes:

Non-disjunction means non-separation of pairs of homologous chromosomes during meiosis. Such case was first reported by Bridges (1913) in Drosophila. He found that sometimes in Drosophila egg the two chromosomes do not separate after synapsis and pass to the same pole, leaving the other without and ‘X’ chromosome.

Hence three kinds of eggs are produced as given below:

(i) Normal eggs, each containing one X chromosome,

(ii) Eggs containing two X chromosomes.

(iii) Eggs without the X chromosomes.

Thus, a quantitative abnormality or unusuality of the X chromosome occurs. White eye colour in Drosophila is a recessive sex-linked character. When a white eyed female is crossed with red eyed male, there is criss-cross of inheritance.

In the F₁ offsprings, males have white eyes and female red eyes. But there are some exceptions and about one in 2000- 3000 F₁ offsprings show red eyes in male and white in female. This has shown to be due to non-disjunction of the X chromosomes.

2. Secondary Non-Disjunction:

All the exceptional males without the Y chromosome are sterile although they are quite males in appearance and in behaviour. However, the white eyed ‘X X Y’ females are normal and fertile. Bridges crossed them to normal red-eyed males and observed in their offspring the secondary non-disjunction. In their progeny about 96% of the daughters have red eyes and 4% white eyes. Among the sons, about 96% are white eyed and 4% red eyed.

During the reduction division in XXY females, the X and Y chromosomes are distributed in different ways and four kinds of eggs are formed.

(i) Eggs with a single X chromosome

(ii) Eggs with a X and a Y chromosome

(iii) Eggs with 2X chromosome

(iv) Eggs with a Y chromosome.

Fertilized by sperms of normal red eyed male, three eggs should produce eight different types of zygotes. 3/8 types of zygotes will not occur with equal frequency. Estimation of the figure shows several ways of testing the validity of this complicated working hypothesis.

All the white eyed female and some of the red eyed ones must carry not only two X chromosomes but also a Y chromosome. Bridges not only made these predictions but verified them by cytological examination of the various classes of the flies.

Non-disjunction of X chromosomes in Drosophila leads to the appearance of zygotes which have one chromosome more (XXX, XXY, XYY) or one chromosome less than normal flies, since the Y chromosome contains relatively few genes, flies with extra Y chromosomes appear to be normal, while males which lack a Y chromosome, differ from normal only in being sterile. On the contrary, the presence of an extra X chromosome (XXY) is usually lethal.

Non-disjunction occurs occasionally not only for the X and Y chromosomes but for other chromosomes as well. It results in the production of zygotes which have one of the chromosomes of the normal complement in triplicate (Trisomies, 2n+1 types) which have chromosomes represented only one instead of twice (Monosomies, 2n-1 types).