The chromosomal theory, linkage and recombination

A home for Mendel's factors

Mendel's laws lay forgotten from 1865 until 1900. By then the microscope had shown how chromosomes behave in meiosis, and in 1902 Walter Sutton and Theodore Boveri saw that the chromosomes behave just like Mendel's factors.

This is the chromosomal theory of inheritance: genes are carried on chromosomes, and the behaviour of chromosomes in meiosis explains the laws of Mendel.

Morgan and the fruit fly

The next steps came from the group of Thomas Hunt Morgan, who worked on the fruit fly Drosophila melanogaster. The fly is a good animal for genetics.

• It grows on a simple synthetic medium in the laboratory.
• Its life cycle is short, about two weeks.
• One mating gives a large number of offspring.
• Males and females are easy to tell apart, and many hereditary variations can be seen with a low power microscope.

Genes on the same chromosome: linkage

Mendel's peas have seven pairs of chromosomes, and the seven traits that he followed assorted independently. A fly or a person has far more genes than chromosomes. So many genes must lie on the same chromosome.

Morgan crossed yellow-bodied, white-eyed female flies with brown-bodied, red-eyed males. In the F2, the parental combinations, yellow with white and brown with red, were far more common than the new combinations. The two genes were not assorting independently. Morgan named the physical association of two genes on one chromosome linkage. The new combinations in the offspring are called recombinants, and the process is recombination.

Genes that are close together are held together more strongly. Genes that lie far apart are often separated.

Crossing over breaks the link

What breaks the link? You know the answer from meiosis. In prophase I, the two homologous chromosomes pair up. Non-sister chromatids exchange pieces. This is crossing over.

Take a plant with the linked genes A and B on one chromosome and a and b on its homologue. Written as AB over ab, it makes four kinds of gamete.

• AB and ab have the same combinations as the parental chromosomes. They are the parental gametes, and they are the common ones.
• Ab and aB carry a new combination. They are the recombinant gametes, and they come only from crossing over between the two genes.

A-Level and IB call the arrangement AB over ab coupling, and Ab over aB repulsion. NCERT does not use these two words.

Recombination frequency and the map

Cross the double heterozygote with a double recessive plant (aabb), a test cross. The double recessive gives only ab, so every offspring shows the gamete that the heterozygote gave.

Suppose that 1000 offspring come out as 430 AaBb, 440 aabb, 65 Aabb and 65 aaBb. The recombinants are 65 + 65 = 130, so the frequency is $130 \div 1000 = 13\%$.

Alfred Sturtevant, a student of Morgan, saw that the frequency can be used as a measure of the distance between two genes. One per cent of recombination is one map unit, also called one centimorgan. A chart of the genes in a line, with the distances between them, is a genetic map.

You get the order of three genes from the three distances. The largest distance is between the two end genes, and it is the sum of the other two. Two cautions follow.

• The frequency of recombination cannot go above 50 per cent. Genes with 50 per cent behave as if they were on different chromosomes.
• For genes far apart, two crossovers can happen between them and cancel each other, so the distances do not add exactly.

NCERT gives two fly examples. The genes for the yellow body and the white eye were very tightly linked and showed very little recombination. The genes for the white eye and the miniature wing showed a high frequency. So the strength of linkage falls as the distance rises.

You should see that at 5 map units almost all the offspring are parental. At 50 map units the four kinds are equal, as if the genes were unlinked.

Try it in Python

The program counts the recombinants of a test cross and finds the order of three genes.

Practise with new numbers

Common mistakes

• Counting the parental classes as recombinants. The recombinants are the two small classes, which differ from both parents.
• Dividing by the number of parental offspring. Divide the recombinants by all the offspring.
• Saying that linked genes never separate. Crossing over separates them, and the farther apart they are, the more often.
• Expecting a recombination frequency above 50 per cent. It cannot be higher, even for genes at opposite ends of a long chromosome.

Remember these

• The chromosomal theory (Sutton and Boveri, 1902): genes are on chromosomes. Morgan worked on Drosophila melanogaster.
• Linked genes lie on the same chromosome and are inherited together. Crossing over makes recombinants.
• Recombination frequency is the recombinants divided by all offspring, in per cent. One per cent is one map unit.
• Sturtevant used the frequencies to make a genetic map. The largest distance of three genes is the sum of the other two.

Check yourself

Try each one on your own first. If you are stuck, open a hint. Then check with Show the answer.

1. Name two points of the behaviour of chromosomes that match Mendel's laws.

2. In a test cross, 44 offspring are AaBb, 46 are aabb, 5 are Aabb and 5 are aaBb. What is the recombination frequency? Which kinds are parental?

3. Gene X is 4 map units from Y, and Y is 6 map units from Z. X and Z are 10 map units apart. In what order do the genes lie?

4. Which of two gene pairs is more tightly linked: one with 2 per cent recombination or one with 30 per cent?

5. Why can a test cross not give more than 50 per cent recombinants?

References

• NCERT (2023). Biology, Textbook for Class XII, chapter 4, sections on the chromosomal theory, linkage and recombination.
• Clark M. A., Douglas M. and Choi J. (2018). Biology 2e, OpenStax, chapter 13.1, Chromosomal Theory and Genetic Linkages.