In this article we will discuss about:- 1. Types of Duplications 2. Origin of Duplications 3. Chromosome Pairing 4. Phenotypic Effects of Duplications 5. Duplications in Human 6. Uses of Duplications.
Types of Duplications:
Broadly, duplications are divided into two types which are further subdivided into different subtypes.
1. Inter-Chromosomal duplication:
The duplicated segment of a chromosome is present in another chromosome of the genome. It is of two types (Fig. 13.1).
(a) The duplicated segment of a chromosome is incorporated into a non-homologous chromosome.
(b) The duplicated segment is present as a separate chromosome. Clearly, it must have a centromere to be able to survive.
2. Intra-Chromosomal duplication:
The duplicated segment remains in the same chromosome. It may be present at different locations (Fig. 13.1).
(a) In the other arm.
(b) In the same arm but removed from the original segment.
(c) In the same arm and next to the original segment. This type of duplication is called tandem duplication which is further subdivided into the following two types. (Fig. 13.1).
(i) Direct tandem:
Gene order of the duplicated segment is the same as that of the original segment.
(ii) Reverse tandem:
Gene order of the duplicated segment is inverted.
Origin of Duplications:
The term duplication was coined by Bridges in 1919, and the first duplications were described in Drosophila melanogaster.
Duplications may originate in the following four ways:
1. Primary structural change of chromosomes
2. Disturbances in the crossing over process (unequal crossing over)
3. Crossing over in inversion heterozygotes
4. Crossing over in translocation heterozygotes and segregation
1. Primary structural change:
A broken segment of a chromosome becomes inserted into its homologue or in a non-homologous chromosome. In 1950, McClintock described the Dissociation-Activator (Ds-AC) system in maize, which is a very remarkable case of genetically governed production of aberrations.
The cytological effects produced by this system include various kinds of chromosomal aberrations, such as, deficiencies, duplications, translocations, inversions and ring chromosomes. The Ds and Ac both are capable of transposition to any chromosome or within the same chromosome. The standard location of Ds is proximal to Wx on chromosome 9 in maize.
When the transposition of Ds takes place, a break occurs at the location it was inserted earlier. Other than this, chromosome breakage occurs either spontaneously or could be induced artificially.
Various kinds of ionizing radiations, such as, X-rays, y-rays, fast and thermal neutrons, and chemical mutagens such as, EMS (ethyl-methanesulfonate), MMS (methyl-methanesulfonate), dES (di-ethyl-sulphate) and EI (ethylene imine) etc. have been used to produce different kinds of chromosomal aberrations.
2. Unequal crossing over:
Deviations from normal chromosome pairing and crossing over processes may occur in specific cases, particularly in heterochromatic regions. This kind of pairing is called heterochromatic fusion or nonspecific pairing, and it may lead to unequal crossing over Sturtevant observed the occurrence of unequal crossing over in D. melanogaster ; it involved the Bar eye locus (Fig. 13.2).
3. Crossing over within inversion:
Crossing over within an inversion produces chromosomes showing deficiency-duplication.
Deficiency-duplication gametes are produced by translocation heterozygotes, but these gametes are sterile. Hagberg in 1965 produced duplications in barley using translocations.
The duplicated segment forms a loop during pachytene in duplication heterozygotes (Fig. 13.3). Unequal crossing over may occur in duplication heterozygotes leading further duplications of the concerned segment. For example, Bar eye locus of Drosophila gives rise to the double-Bar (ultra bar) eye following unequal crossing over; conversely, double-Bar may revert to Bar due to unequal crossing over (Fig. 13.2).
Reverse tandem duplications may form a loop to pair with the normal chromosome. A crossing over within the loop produces a dicentric chromatid bridge at AI (Fig. 13.4). In some cases, the duplicated segment of the chromosome folds back to pair with the original segment present in the same chromosome.
A crossing over within this paired segment produces a loop at AI which gives rise to a dicentric chromatid bridge in one cell of the dyad at All (Fig. 13.5). In 1941, McClintock obtained a reverse tandem duplication in the short arm of chromosome 9 of maize; this segment included the genes for colourless aleurone (c), shrunken endosperm (sh) and waxy pollen (wx).
As a result of chromosome pairing, dicentric chromatids were produced which formed dicentric bridge at AI (Fig. 13.4). The AI bridge was broken, and chromosomes having smaller or larger deficiencies and duplications were produced depending on the position of the break.
During the following interphase, when the chromosomes replicate, the broken ends of the sister chromatids may unite and form dicentric bridge at the subsequent anaphase. This will lead to a “breakage-fusion-bridge” cycle. In corn, the breakage-fusion-bridge cycle continues through the successive cell divisions in the gametophyte as well as in the endosperm but not in the embryo.
Phenotypic Effects of Duplications:
(1) Duplications may produce specific effects when the phenotype is affected due to a change in the position of a gene; it is called position effect.
The position effects are of two types:
(i) Stable type or S-type (cis-trans type), and
(ii) Variegated type or V-type.
An example of the stable type of position effect is the “Bar-eye” phenotype of Drosophila. The Bar eye phenotype is the result of a duplication of the 16A region of the X chromosome (Fig. 13.6). The 16A region contains 5 bands, two of which are doublets. In the case of the Bar eye phenotype; the number of facets in the compound eye of the adult fly is reduced from the normal 779 to only 358 in case of heterozygous bar (BB+).
But in homozygous bar flies (BB) the average number of facets is further reduced to 68. Three repeats of the 16A region produces the ultra-Bar or double-Bar phenotype, in which the number of facets is greatly reduced; it is reduced to only 45 in the case of heterozygous double-Bar, and to only 25 in the case of homozygous double-Bar. The type of position effect is related to the euchromatic regions of chromosomes.
The V-type position effects are confined to the genes present in the heterozygous state. It is the result of a partial repression through heterochromatinization when the functional allele of the gene is brought close to heterochromatin. The wild type allele expresses like a mutant allele due to the heterochromatinization.
However, the normal allele may escape repression due to heterochromatin in many cases and a variegated phenotype (a mixture of wild type and mutant type sectors) is produced. Such type of position effects is produced by structural changes like translocations and inversions.
(2) Duplication may lead to a more intense effect of the duplicated gene. In the breakage- fusion-bridge cycle, the gene C (for coloured endosperm) becomes duplicated in some cells, while some other cells lose this gene. The latter cells produce colourless sectors, while the former give rise to coloured sectors (twin sectors). Further, bridge-break-fusions produce spots in the endosperm with different colour intensities.
(3) The activity of certain enzymes is increased by a duplication of the concerned gene. Hagberg, in 1965, obtained a duplication for a short segment of the chromosome 6 of barley; the plant having this duplication showed the doubled activity of the enzyme a-amylase.
Other Effects of Duplications:
In Drosophila, deficiency of the band 3C7 results in the notch phenotype, but its duplication produces the “abruptex” (Ax) phenotype. Abruptex is characterized by short, thin and arched wings: veins not reaching the margin, presence of fewer hairs on thorax and head, and bald patches. In Drosophila, other example exists where duplications produce dominant phenotypic effects.
Hairy wing (Hw) is due to a tandem repeat of two bands, band lB1.2, of the X chromosome. Hairy wing males have extra hairs and bristles along the wing veins on the head and on their thorax; this effect is more pronounced in females. Another phenotype “confluence” (Co) is associated with tandem duplication of the bands 3C5 to 3D6; this phenotype is characterized by thickened and delta like ends of the wing veins.
Duplications are believed to have played an important role in evolution. In Drosophila where salivary gland polytene chromosomes can be analysed accurately, numerous duplicated segments have been identified. Similarly, in many plants, many duplicated loci have been investigated. The duplicated segments may be large or very small. Duplications are proposed to have given rise to new gene functions.
The duplicate and polymeric factors are considered to represent duplications. The several types of haemoglobins in man and animals are believed to have originated through duplication of a common ancestral gene. In 1970, it was suggested by Ohno that the duplications are responsible for effective evolution by increase in DNA content per cell; in’ conjunction with mutation, it gives rise to new genes.
The latter is achieved because duplication provides additional copies of genes which can go on accumulating mutations (in the duplicated copies of the genes) without any deleterious effect on the organisms, since a fully functional copy of the concerned genes is always available. In due course of time, the accumulation of mutations changes the duplicate copies to the extent that they may ultimately assume new functions.
Duplications in Human:
In human, duplication-deletion syndrome has been reported by some workers. Duplication has been reported to be produced to a crossing over in a pericentric inversion involving the chromosome 3. The main features of this duplication were facial dismorphy and congenital anomalies.
Uses of Duplications:
(1) Duplications can be used to study the chromosome behaviour during meiosis, such as, chromosome pairing, crossing over and their consequences.
(2) Duplications offer a number of possibilities in plant breeding. They can be used to increase the dosage of certain desirable genes for increasing disease or pest resistance, enzymatic activity or other characteristics. For example, the activity of the enzyme alpha-amylase in grains of barley is greatly increased due to a duplication in the short arm of chromosome 6.
Duplication has an advantage over polyploidy because the genetic dis-balance due to the duplication of chromosomal segments is lesser as compared to polyploidy where the whole genome is duplicated.
(3) In case where genes for resistance to diseases or pests are linked to some undesirable genes or the genes for resistance to various races are allelic, a combination of resistance to different races can be obtained through duplication.
(4) True breeding heterosis may be established in self-fertilized crops by the technique of duplication breeding. Homozygous duplications in the heterozygous condition for the heterotic loci will give rise to permanent hybrid vigour.
(5) Duplication may be used to study the dosage effect of the nucleolar organizer.
(6) Duplications may be useful in the study of the position effects.
(7) New genes can be produced only through duplications; thus it is believed to have played an important role in evolution.