The below mentioned article provides a study note on the Linkage of Genes.
When Mendel’s work was rediscovered, thousands of experiments were conducted by the early biologists on the diverse groups of plants and animals. The results obtained in those cases were quite contrary to the principles of independent assortment, but none of the interpretations was good enough to justify for an alternative hypothesis to Mendel’s principle of independent assortment.
Sutton and Boveri noted that chromosomal behaviour in meiosis at the time of gametogenesis paralleled the genetic events described by Mendel. They concluded that the genes (hereditary factors or units) must be located in or on the chromosomes.
Mendel’s choice of the seven pairs of characters was indeed fortunate one, for the garden pea has seven pairs of chromosomes and each of the seven pairs of characteristics was associated with a different pair of chromosomes.
William Bateson and R.C. Punnett (1906) reported a dihybrid experiment in sweet pea (lathyrus odoratus) where segregation ratio could not be explained by Mendel’s law of independent assortment. They crossed purple flowered and long pollen grained sweet pea with another variety of sweet pea which had red flowers and round pollen grains.
The purple colour of the flower (r) and long pollen grains (1) had been proved by previous experiments to be governed by separate genes and were dominant over red colour of the flower (r) and roundness (1) of pollen grains respectively. So, as expected, in F1, they found all hybrid plants with purple flowers and long pollen grains.
When F1, plants were self-pollinated a wide divergence was noted in F1 generation from the expected normal dihybrid ratio, i.e., 9: 3: 3 : 1.
W. Bateson and R.C. Punnett were the first to observe that two pairs of genes did not necessarily assort independently of each other. But they believed that the genes were not located on chromosomes and so rejected the chromosome theory. To explain their results they proposed that independent assortment had occurred but was followed by differential sex reproduction.
That is to say, during gamete formation, the cells containing both dominant (r+1+) and both recessive (rl) genes underwent mitotic reproduction to a greater extent than the others thereby giving specific ratio. This is reduplication hypothesis.
Bateson and Punnentt performed another cross in which they took a sweet pea plant with purple flower and round pollen (r+1+ll) and another plant with red flower and long pollen grain (rr1+1+). The F1, as expected, were with purple flowers and long pollen grains (r+ rl+1) which on selfing produced F2 plants.
The segregation in F2 generation was again not in way as could be expected from the normal dihybrid ratio i.e., 9:3:3:1.
Coupling and Repulsion:
Bateson and Punnett pointed out that when two or more dominants entered from same parents they tended to remain together and did not assort independently so that the recombinants were fewer than the parental types. Similar was the case with recessive alleles also.
Bateson and Punnett called this tendency of both dominants or both recessives introduced in the cross by the same parents to remain together in subsequent generation more often as “coupling”.
Conversely, it was found that two dominant genes introduced in the cross by different parents, as shown in the second experiment tended to remain apart in subsequent generation. This is called repulsion.
Thus if a chromosome carries two genes A and B and its homologue carries recessive alleles a and b, A and B are said to be in coupling. Possibilities are also there that in a chromosomal pair, one contains genes A and b and its homologue contains a and B. In such a condition A and B genes are in repulsion.
Two other terms cis and trans have also been used to denote coupling and repulsion respectively. The theory of coupling and repulsion is now discarded. Actually, Bateson and Punnett did not relate the mechanism with the chromosomes. Thus they missed true explanation by the narrow margin.
This discrepancy or abnormality in the earlier mentioned dihybrid result was explained in 1910 by Thomas Hunt Morgan who found similar gene behaviour in drosophila melanogaster while studying the behaviour of two different gene pairs. One gene pair affects eye colour (pr responsible for purple eye and pr+ for red eye) and the other pair affects wing length (gene vg responsible for vestigial and vg+ for normal wing).
He crossed flies with prpr vgvg and pr+ pr+ vg+ vg+ and then test-crossed F1, females prpr+vgvg+ with prpr vgvg male and obtained the following results:
Obviously, this is a drastic deviation from the expected 1:1:1:1 ratio of a dihybrid test cross and again indicates coupling of genes. The most common classes are the two gene combinations pr+ vg+ and pr vg originally introduced by parental flies.
A cross between two parental types with genotypes pr+ pr+ vg+ vg+ and pr + pr vg+ vg (each parent being homozygous for one of the recessive genes) produced F1, individuals with genotype pr+ pr+ vg +vg and the test cross pr+ pr vg+ vg ♀× pr vgvg ♂ gave a different result.
Again the results of that test cross were not close to 1: 1: 1: 1. The test cross is very important cross for determining whether the two genes are associated or independent of each other. When there is significant deviation from 1:1:1:1 ratio so that too many parental genotypes and too few recombinant genotypes are found, the two genes in question are considered to be associated.
In order to explain his results T.H. Morgan established the theory of genes and very clearly explained the role of chromosomes in inheritance of characters. According to gene theory of Morgan the chromosomes are the bearers of genes and the genes are arranged on the chromosomes in linear order.
Morgan suggested that the two pairs of genes under study were present on the same pair of homologous chromosomes. The tendency of genes to be inherited in group is known as linkage.
To explain this phenomenon Morgan and Castle advanced a linkage hypothesis which states that:
(i) Chromosomes are the bearers of hereditary units, the genes.
(ii) Genes are arranged on the chromosomes in linear order.
(iii) Genes located on the same chromosome are said to be linked and the chromosome as such is a linkage group. Thus, there are as many linkage groups in a cell as are the pairs of chromosomes.
(iv) Each gene has a definite position (locus) in the chromosomes.
(v) The distance between linked genes determines the degree of linkage strength. The closely located genes show strong linkage while the widely located ones show weak linkage.
(vi) Closely linked genes more often tend to remain in original combination in the course of inheritance (complete linkage) but some-times genes change linkage groups in some meiotic cells because of exchange of chromosome segments).
Morgan showed that coupling and repulsion were the two distinct aspects of the single phenomenon to which he called linkage. Thus when pr and vg genes were introduced from one parent they were physically located on the same chromosome and similarly pr+ and vg+ on the homologous chromosome from the other parent.
This hypothesis would apply to repulsion as well where one chromosome of a parent carries pr and vg+ and the other homologous chromosome has pr+ and vg. This explains why parental gene combinations remain together.
In order to explain the non-parental gene combinations, Morgan suggested that when homologous chromosomes pair during meiosis, there is occasionally a physical exchange of chromosome segments by a process called crossing over which results in new combination.
The mechanism will be clear in foregoing discussion. The original parental gene arrangement on the homologous chromosomes is called parental combination and the new gene combinations arising out of crossing over are called cross over types or exchange products or recombinants.
This hypothesis was later confirmed by F. Janssen who reported his observations on meiotic chromosomes in amphibians and orthopterans and suggested a cytological basis for crossing over. Jansens often noticed that during meiosis when duplicated homologous chromosomes were paired two non-sister chromatids crossed each other while the other two did not.
He termed such cross (X) shaped configuration as chiasma (plural chiasmata). Chiasmata are just what one might expect cross over events to look like. It was not until 1921 however that Bateson abandoned his hypothesis in view of the sufficient counter evidences.
It is an established fact that the hereditary genes which determine the characters of the individuals are carried in the chromosomes of the germ cells. When organisms were studied for their chromosome number and also for number of Mendelian traits, it was found that the gene number far exceeded the number of chromosomes.
As in the organism, number of genes is greater than chromosome number, it can be expected that each chromosome contains many genes.
The genes that are located in the same chromosomes are linked to it and would be expected to be inherited as a single group. Thus each chromosome is linkage group.
There are as many linkage groups as there are pairs of chromosomes, for example 4 for drosophila melanogaster, 23 for man, 10 in maize and so on. Since the chromosomes ordinarily duplicate at the time of gamete formation, all the genes present on a particular chromosome will be transmitted to the gamete as single block or unit.
The random assortment will not take place between genes borne in the chromosomes. This phenomenon is known as linkage. The linkage is not due to any relation between two genes but is simply because they happen to be located in the same chromosome.
Experimentally, it has been found that linked genes are not always inherited as single unit, but nearly they tend to remain together. It has also been observed experimentally that larger the chromosomes larger will be the number of genes on them. Small chromosomes have got small number of genes.