The below mentioned article provides note on multiple alleles.
After Mendel first advocated the existence of two factors for each character, it was demonstrated in many organisms that a gene consists of a pair of alleles. Each member of the pair of alleles is said to occupy an identical position or locus on each of the two homologous chromosomes in diploid cells of an organism.
In Mendel’s experiment the gene controlling height of pea plants has both its alleles designated either as T and T or T and t, or t and t. Since there are always only two alleles they can also be denoted as T1 and T2. Similarly the gene determining flower colour (R and r) can be denoted by alleles R1 and R2.
Sometimes more than two alternative alleles or multiple alleles are present in different individuals of a population. When there are multiple alleles, a gene is denoted by more than two alleles such as T1, T2, T3, T4 and R1, R2, R3, R4,…… and so on.
Now there are only two homologous chromosomes in a diploid cell, and at one particular site of a gene or locus, only one allele can be present. Therefore, in one diploid cell only two alleles are present at a particular locus. In other members of the population, due to two or more mutations, the same locus on two homologous chromosomes could have two different alleles.
In this way it is possible to detect a number of alleles for one gene from their different expressions in different individuals. Such a system in which one gene has more than two allelic states at the same locus in different members of the population is known as a multiple allele system.
T.H. Morgan in 1910 described the first case of multiple alleles of a gene controlling eye colour in Drosophila during his studies on mutation. In a vial of flies with normal red eyes he found a fly with white eyes which had arisen due to a mutation in the gene which produces red colour in normal flies.
By performing genetic experiments, the position of this gene was determined to be on the X chromosome, the exact location being 1.5 units from the left end of this chromosome.
This location is identical to the position occupied by the gene which produces red colour in eyes. Later on some other flies were discovered with eye colour resembling the biological stain eosin. The gene for eosin colour was also found to be located at 1.5 units on the X chromosome.
When crosses were made between eosin flies and red, and between eosin and white it turned out that the gene for eosin was an allele to both red and white genes. This proves that genes producing red, white and eosin eyes in different flies are all alleles of each other. In other words the gene controlling eye colour in Drosophila has multiple alleles.
Later on a series of alleles producing eye pigments in different shades and intensities between red and white were found; each shade has a different name such as wine, blood, coral, cherry, apricot, honey, pearl and ivory, and a few more. It also means that the different alleles become less and less efficient in producing the same kind of biochemical product.
Sometimes phenotypes produced by different alleles are not markedly different so that some of them appear close to the normal red. Such alleles with similar effects are referred to as isoalleles. There are wild- type isoalleles for genes expressing the wild phenotype. The mutant gene for white eye colour in Drosophila is composed of a series of multiple isoalleles W1, W2, W3 etc. These are known as mutant isoalleles.
The Himalayan rabbit is a classic example for illustrating multiple alleles, first studied by Sturtevant in 1913. The wild type rabbit has grey fur and is called agouti; rabbits with all white fur and pink eyes are albino; the Himalayan has white fur on the body, but its feet, tail, ears and tip of nose are black (Fig. 5.1). When crosses were made between agouti and albino, and between agouti and Himalayan, both albino and Himalayan were found to behave as recessive to agouti.
When Himalayan and albino were crossed, F1 were all Himalayan, and in F2 3 Himalayan: 1 albino were produced. Clearly, Himalayan, agouti and albino all result from different alleles of the gene that controls fur or coat colour in rabbits. If C denotes the dominant allele that produces the wild agouti type of fur, then albino would have the genotype cc.
The cross of agouti (CC) and Himalayan (ch ch) would give an F2 consisting of 3 agouti (CC, Cch) and one Himalayan (ch ch). Similarly, the cross between Himalayan and albino (cc) would give an F2 of 3 Himalayan (chch, chc) and one albino (cc). There is also a fourth allele for fur colour in rabbits called chinchilla (cch) which behaves like Himalayan.
Multiple Alleles and Complex Loci:
So far we have considered multiple alleles as a series of alternative forms of a gene present at the same locus. The earlier concept of genetic recombination implies crossing-over between genes, not within a gene. The idea was based on breakage and exchange of segments of paired homologous chromosomes, resulting in new linear arrangements of genes.
Genetically it could be observed in the test-cross progeny of a heterozygote and a homozygous recessive; the frequency of recombinant phenotypes was used for gene mapping. The two genes involved in recombination must obviously occupy different loci.
In 1942, Oliver showed that in the case of lozenge eye alleles in Drosophila, crossing over could occur between alleles present in the same locus. But because at that time the gene was thought to be an indivisible unit, his view was not accepted.
Lewis found some other mutants in Drosophila which behaved in the same ways as the lozenge eye mutants. Since they could produce recombinant progeny in test crosses, due to crossing over between two mutant sites in a locus, it became doubtful that they were true alleles. The term pseudo-alleles was coined for such alleles.
The earlier concept of genes arranged like beads-on-a string had to be revised. A gene is a sequence of nucleotides in DNA that controls a specific gene product. The different mutations of the gene may be due to changes in single nucleotides at more than one locations in the gene. Crossing over could take place between the altered nucleotides within a gene.
Since the mutant nucleotides are placed so close together, crossing over is expected with a very low frequency. When several different genes which affect the same trait are present so close that crossing over is rare between them, the term complex locus is applied to them.
The term multiple alleles can also be redefined in the following way. Within the nucleotide sequence of DNA that represents a gene, multiple alleles are due to mutations at different points within the gene.