Linkage

Linkage

In his classic paper, Mendel reported the results of crosses involving alleles of seven genes that controlled seven different phenotypic characteristics of the garden pea. The observed segregation of the two alleles of each gene was the basis of Mendel’s first law  - law of segregation. When Mendel crossed pea plants differing in two phenotypic characteristics, so-called dihybrid crosses, the segregation of the alleles of the second gene occurred independently of the segregation of the alleles of the first gene. This provided the basis of Mendel’s second law – the law of independent assortment.

Mendel’s paper detailed the results of his hybrid cross between pea plants with yellow, round seeds and pea plants with green, wrinkled. The genes controlling this two traits, yellow versus green seed color and round versus wrinkled seed shape, are now known to be located on chromosomes 1 and 7, respectively, of the garden pea. Had these traits been controlled by genes located near one another on the same chromosome, Mendel would not have observed the independent assortment of the alleles of these genes, and , thus, would not have been able to deduce his second law from the result of this cross.

Combinations of alleles of each of the segregating  genes that are present on a particular chromosome of the parents tend to remain together on that chromosome in the progeny. That is, such alleles behave as though they are partially linked.

Clearly, each chromosome must contain many genes, and these genes would not be expected to assort independently, since, the basis of the independent assortment is the independent segregation of different pairs of homologous chromosomes during the reductional division of Meiosis.

In 1905, William Bateson and R.C Punnet investigated the inheritance patterns for various traits in the sweet pea, Lathyrus odoratus. Plants of sweet pea variety having blue flowers (BB) and Long Pollen (LL) were crossed with those of another variety having red flowers (bb) and round pollen (ll). F₁ individuals had blue flowers and long pollen (BbLl).

The F₁ plants were test crossed with the recessive parent (red flowers and round pollen, bbll). Normally, if independent assortment takes place, we should expect 1:1:1:1 ratio in a test cross. Instead, 7:1:1:7 ratio was actually obtained, and they found many more phenotypes like the original parents ( blue, long and red, round) and many fewer single dominant or non-parental types blue, round and red, long), indicating that there was a tendency in dominant alleles to remain together, similar was the case with recessive alleles.

Bateson and Punnett suggested that because the two parental phenotypes were in excess in F₂ progeny, there might be a physical connection between the parental alleles. This tendency of the alleles coming from the same parent to enter the same gamete and to inherit together was termed as gametic coupling by Bateson and Punnett.

Bateson and Punnett made another cross which involved the same characters but in a different combination. A sweet pea plant bearing blue flowers and round pollen (BBll) was crossed with another plant having red flowers and long pollen (bbLL).

The F₁ plants were found to be heterozygous blue, long (BbLl). The F₁ hybrids when test crossed with recessive (bbll) parent, progeny appeared in 1:7:7:1 ratio instead of 1:1:1:1 ratio.

 

  

The results show that the two dominant genes (B and L) or recessive genes (b and l ) repelled each other because they came from different parents. The gametes with genotypes Bl and bL were formed in more number. Hence, the blue, round and red, long plants were produced in more number. This peculiarity was called Repulsion by them.

Morgan’s concept of Linkage:

A Mechanistic explanation for Bateson and Punnett’s observation come later from the research of T.H Morgan, using two genes in Drosophilla. One gene affected eye colour (recessive purple, pr, and dominant wild type red pr⁺, ) and the other gene affected wing development (recessive vestigial, vg, and dominant normal vg⁺).

Morgan crossed a red eye and normal winged Drosophilla with a purple eye and vestigial winged. F₁ progeny were heterozygous for red eye and normal winged. He then, test crossed the F₁ progeny. He got 7:1:1:7 ratio. The number of parental phenotypes were many times more than those of non-parental phenotypes, indicating that the independent assortment hypothesis does not hold up.

In second experiment, Morgan crossed two different genotypes, each of which was homozygous for a wild-type allele at one gene and homozygous for a recessive allele at another gene (pr⁺ pr⁺, vg vg) X (pr pr, vg⁺  vg⁺). The F₁ progeny were doubly heterozygous for red eye, normal wing and purple eye, vestigial wing, pr⁺ pr, vg⁺ vg).

The F₁ progeny were test crossed with pr pr, vg vg. He got a ratio of 1:7:7:1. In this cross, the progeny numbers in the F₂ of the single dominants and double recessive were much lower than expected. In other words, there were more repulsion types than coupling types.

To explain his observations, Morgan suggested that the genes for these two traits are on the same chromosome.  Two genes are found to be in coupling phase (on same chromosome) or in repulsion phase (on two different but homologous chromosomes).

Alleles of two genes tend to remain associated because they are physically linked to each other. Genes that are on the same chromosome are said to be linked, and the tendency of these genes located on a same chromosome to remain together and inherit as single unit is called linkage.

Morgan further suggested that the strength of linkage will be determined by distance between two genes in question. The greater the this distance, lower will be the linkage strength. This linkage is broken down due to the phenomenon of crossing over occurring during meiosis. Crossing over will be relatively more frequent, if distance between two genes is more and in a case where the distance between tow genes is less, it is less frequent.

Chromosome Theory of Linkage:

Morgan and Castle have formulated the Chromosome Theory of  Linkage. It states that:

1.      Genes located in the same chromosome are inherited together and show linkage.

2.      The linked genes are arranged in a linear fashion in the chromosome

3.      The degree of linkage is determined by the distance between the two genes. Linkage strength is inversely proportional to the distance between the two genes. Closely related genes show strong linkage, while genes widely located show weak linkage.

4.      Linked genes show two types of arrangement in heterozygous individuals:

Cis-arrangement: the dominant genes of both the pairs (A and B) are located in one member of the chromosome pair and their recessive alleles (a and b) are located in the other chromosome of the pair. The heterozygotes with such arrangement are known as Cis – heterozygotes. In such cases, the genes are said to be in coupling phase.

Trans – arrangement: the dominant gene of one pair and the recessive gene of the other pair are located on one chromosome. The recessive gene of the first pair and the dominant gene of the second pair are located in the second chromosome pair (Ab/aB). This arrangement of one dominant and one recessive gene in the same chromosome of the homologous pair is known as tran-arrangement and the heterozygotes with such arrangement are called trans – heterozygotes. In such case, the genes show repulsion.

Linkage groups:

            All the genes which are located on the same chromosome constitute a linkage group. The number of linkage groups of a species, is equal to the haploid chromosome number of that species. This is because, the homologous chromosomes show identical genes.

Examples:

            Drosophilla has 4 pairs of chromosomes and 4 linkage groups

            Humans have 23 pairs of chromosomes and 23 linkage groups.