Genetic Linkage-Introduction, types, and chromosomal theory of linkage

Introduction:

All the situations and examples discussed with inheritance of character according to Mendel’s law are inheritance of genes situated on different chromosomes.
Cytological study have reveals that human possess 46 chromosomes in all somatic cells (Vegetative cells). Since human possess thousands of characters such as blood group, eye color, insulin production etc, it follows that each chromosome must carry a large number of genes.
Genes situated on same chromosome are said to be linked. All genes on a single chromosome form a linkage group and usually pass into same gamete and are inherited together.
According to Mendel’s law of independent assortment, the genes situated in different chromosomes assort and appear independently in next generation either appear together or apart.
But if the genes are situated in the same chromosome and are fairly close to each other, they tend to be inherited together. This type of inheritance of linked genes in the same chromosome is known as Linkage.
As a result of linkage, genes belonging to the same linkage group usually do not show independent assortment. Since these genes do not conform to Mendel’s principle of independent assortment they fail to produce the expected 9:3:3:1 ratio in a breeding situation involving the inheritance of two pairs of contrasting characters (Dihybrid cross). In linkage, a variety of ratios are produced.

In most breeding experiments involving linkage produces approximately equal numbers of parental phenotypes and a significant smaller number of recombinant phenotypes (new combination of characters) in equal numbers.

Therefore, two genes are said to be linked when phenotypes with recombinant characters occur less frequently than the parental characters.

The theory of chromosomal inheritance of linked gene was proposed by T. H Morgan in 1911 as experiments shows linked genes in a same chromosome tend to remain in their original combinations.
Before Morgan, W. Sutton and T. Boveri 1902), Sutton (1903) and Bateson and Punnett (1906) had put forward some hypothesis about the phenomenon of linkage.

Coupling and Repulsion hypothesis of linkage: by Bateson and Punnett

Bateson and Punnett in 1906 described a cross in sweat pea (Latharus odoratus), where they find gene pairs do not assort independently as expected.
While they were working on sweet pea, they noticed two variety of plant-plant with Blue flowers (BB) with long pollen grains (LL) and red flower (bb) with round pollen grain (ll).
When the sweat pea variety having blue flower and long pollen grain (BBLL) were crossed with those of another variety having red flower and round pollen (bbll).
In F1 generation, all the offspring having blue flower and long pollen (BbLl) were observed as expected. Because, blue color is dominant over red and long pollen is dominant over round.
When these F1 offspring (BbLl) were test crossed with red flower and round pollen variety (bbll), they obtained (BbLl), (Bbll), (bbLl), (bbll) in the ration 7:1:1:7 instead of 1:1:1:1.
This indicates that the dominant characters (Blue color and long pollen) tends to remain together. Similarly, the recessive characters (red color and round pollen) tends to remain together. This deviation or phenomenon is explained by Coupling and Repulsion hypothesis by Bateson and Punnett.
Bateson and punnett conclude that- the pairs of genes from homozygous parents try to remains together in a cross due to which parental characters is more frequent. This is due to coupling. Two dominant gene for Blue flower and long pollen (BL) are linked in one plant while in other plant two recessive gene for red flower and round pollen (bl) are linked. Such linkage is called coupling.
In another experiment, when a cross was made between sweet pea variety having blue flower and round pollen (BBll) with another variety having red flower and long pollen (bbLL)
In F1 generation, all offspring with blue flower and long pollen were obtained (BbLl).
When these F1 offspring (BbLl) were test crossed with red flower and round pollen variety (bbll), they obtained (BbLl), (Bbll), (bbLl), (bbll) in the ratio 1:7:7:1 instead of 1:1:1:1.
It was observed in both experimental cases that plants with parental characters are obtained in excess number than the plants with recombinant characters. Also when dominant alleles are from different parents (heterozygous ) the frequency of recombination is more because of repulsion of gene (repulsion).
In First experiment, BL are linked and such linkage is known as Coupling and in second experiment bL are linked and such linkage is known as Repulsion.
The coupling and repulsion hypothesis is now discarded.

Chromosomal theory of linkage: by T. H Morgan

Bateson and Punnett failed to explain the exact reasons of coupling and repulsion
Later, T.H. Morgan who found coupling and repulsion hypothesis incomplete, while performing experiments with Drosophila, in 1910. Therefore, he proposed that the two genes are found in coupling phase because they are present on same chromosome and similarly on repulsion phase because they are preset on two different homologous chromosomes. There genes are then called linked genes and the phenomenon of inheritance of such linked genes is called linkage by Morgan.
And the term coupling and repulsion were replaced by the terms, cis and trans by (Haldane, 1942).
Morgan stated the linked genes have the tendency to remain together in original combination because they are located on same chromosome. And the strength of linkage depends upon the distance between the linked genes in the chromosome.
The concept of linkage by Morgan establish the foundation of Cytogenetics and develop the theory of linear arrangement of genes in the chromosomes and helps to construct genetic map of the chromosome.
According to Chromosomal theory of linkage:
Chromosome contains genes and Genes lie in a linear order in a chromosome and distance between them is variable.
- Each gene has a definite locus in a chromosome. The genes which are close to each other, shows the phenomenon of linkage
- The linked genes cannot be separated during gametogenesis (inheritance process), they inherited together
- Tendency of genes to remain linked is due to their presence on same chromosome
- The distance between the linked genes determines the strength of linkage. The closer the distance stronger is the linkage strength.
- The linkage is not due to any relation between two genes but is simply because they happens to be located in the same chromosome

Linkage group:

Genes situated on a chromosome are linked and all the genes on a single chromosome forms a linkage group. The gene located in different chromosome are unlinked genes.
Usually linkage group as a whole passes into gamete during gametogenesis and are inherited together.
The number of linkage group is equal to total number of chromosome in a cell. But actual number is restricted to haploid number of chromosome
Human has 23 pairs of chromosomes and 23 linkage groups.
- Male: 22 autosome + X-chromosome + Y chromosome= 24 linkage group
Drosophila has 4 pairs of chromosomes and 4 linkage groups.
Maize (Zea mays) has 10 pairs of chromosomes and 10 linkage groups.

Types of Linkage:

There are two types of linkage; complete linkage and incomplete linkage

Complete Linkage:

When genes are very closely associated to each other, they tends to remains together and have no chance of separation from each other during inheritance. These genes are called linked genes and the phenomenon is known as complete linkage.
In complete linkage the parental combination of characters appear together for two or more generations in a continuous and regular fashion.

Examples:

Red eyed Normal winged Female Drosophila (RRWW) crossed with purple eyed vestigial wing male Drosophila (rrww).
In F1 progeny, all the Drosophila obtained were heterozygous with red eyed normal winged (RrWw)
When F1 males (RrWw) were test crossed to homozygous recessive female (rrww), only two types of F2 progeny individuals were produced (one type with red eyed normal winged (RrWw) and other type with purple eyed vestigial winged (rrww) in ratio 1:1 ).
Recombinant type are absent. Frequency of recombination is Zero
This is due to complete linkage between gene for eye color and wings. The F1 males produced only two types of gametes ie (RW) and (rw) instead of all possible four types of gametes.
In most of the organism, crossing over takes places during gametogenesis. But in male Drosophila and in female Silkworm, the frequesncy of crossing over is either very area or not at all.
Because of this, linked genes remains together during inheritance, showing complete linkage phenomenon.
However, in practice, total linkage is rare.
When F1 males were crossed with F1 females, the ratio would be 3:1 of parental characters. However, in practice 3:1 ratio never achieve, this is because total linkage is rare.

Incomplete Linkage

The linked genes which are located at farther distance in a chromosome, do not always remains together and separate during gametogenesis are said to be incompletely linked gene and the phenomenon is known as Incomplete linkage.
These linked genes separates because of crossing over between the homologous non-sister chromatids during pachytene stage of Prophase-I of meiosis.
The incomplete linkage have been reported in various organisms including female Drosophila.