WHAT ARE LINKED GENES? (BIOLOGY) - BIOLOGY - 2025

Two genes are linked when they tend to be inherited together as if they were a single entity. This can also happen with more than two genes. In any case, this behavior of the genes is what has allowed genetic mapping by linkage and recombination.

In Mendel's time, other researchers, such as the Boveri spouses, had observed that in the nucleus of the cell there were bodies that secreted during the process of cell division. These were the chromosomes.

Later, with the work of Morgan and his group, there was a clearer understanding of the inheritance of genes and chromosomes. In other words, genes segregate like the chromosomes that carry them (chromosomal theory of inheritance).

Human and genes

There are, as we know, far fewer chromosomes than genes. The human being, for example, has about 20,000 genes distributed in about 23 different chromosomes (haploid load of the species).

Each chromosome is represented by a long DNA molecule in which many, many genes are separately encoded. Each gene, then, resides at a particular site (locus) on a specific chromosome; in turn, each chromosome carries many genes.

In other words, all the genes on a chromosome are linked to each other. If it seems that they are not, it is because there is a process of physical exchange of DNA between the chromosomes that creates the illusion of independent distribution.

This process is called recombination. If two genes are linked, but widely separated from each other, recombination will always occur and the genes will segregate just as Mendel observed.

Ligation

To observe and demonstrate linkage, the investigator proceeds to crossbreed individuals with a contrasting manifestation of the phenotype of the genes under study (for example, P: AAbb X aaBB).

All F1 descendants will be AaBb. From the AaBb X aabb dihybrid cross (or test cross) one would expect an F2 offspring showing the genotype (and phenotypic) 1 AaBb: 1 Aabb: 1 aaBb: 1 aabb ratios.

But this is only true if the genes are not linked. The first genetic clue that two genes are linked is that there is a predominance of the paternal phenotypes: that is, Aabb + aaBb >> AaB_b + aabb.

Repulsion and coupling

In the case of linked genes that we use as an example, individuals will produce mostly Ab and aB gametes, rather than AB and ab gametes.

Since the dominant allele of one gene is associated with the recessive allele of the other gene, the two genes are said to be linked in repulsion. If a predominance of the AB and ab alleles over the Ab and aB gametes is observed, the genes are said to be linked in coupling.

That is, the dominant alleles are coupled to the same DNA molecule; or what is the same, they are associated with the same chromosome. This information is extremely useful in genetic improvement.

This makes it possible to establish the number of individuals that must be analyzed when the genes are linked and it is desired to select, for example, the two dominant characters.

This would be more difficult to achieve when both genes are in repulsion and the linkage is so tight that there is almost no recombination between the two genes.

Linkage disequilibrium

The existence of linkage itself was a huge advance in our understanding of genes and their organization. But in addition, it also allowed us to understand how selection can act in populations and explain a little the evolution of living beings.

There are genes that are so closely linked that only two types of gametes are produced instead of the four that would allow independent distribution.

Linkage disequilibrium

In extreme cases, these two linked genes (in coupling or in repulsion) only appear in one type of association in the population. If this occurs, it is said that there is a linkage disequilibrium.

Linkage disequilibrium occurs, for example, when the lack of the two dominant alleles decreases the chances of survival and reproduction of individuals.

This occurs when individuals are the product of fertilization between ab gametes. The fertilization between gametes aB and Ab, on the contrary, increases the probability of survival of the individual.

These will have at least one A allele and one B allele, and will show corresponding wild-type associated functions.

Linkage, and its disequilibrium, can also explain why some undesirable alleles of a gene are not eliminated from the population. If they are closely linked (in repulsion) to dominant alleles of another gene that confers advantages on its carrier (for example, aB), being associated with the "good" allows the permanence of the "bad".

Recombination and linkage genetic mapping

An important consequence of linkage is that it enables the distance between linked genes to be determined. This turned out to be historically true and led to the generation of the first genetic maps.

To do this, it was necessary to understand that homologous chromosomes can cross each other during meiosis in a process called recombination.

When recombining, different gametes are produced to those that an individual could produce only by segregation. Since recombinants can be counted, it is possible to express mathematically how far apart one gene from another.

In linkage and recombination maps, individuals who are recombinant between a particular gene pair are counted. Then its percentage is calculated in terms of the total mapping population employed.

By convention, one percent (1%) recombination is a genetic map unit (umg). For example, in a mapping population of 1000 individuals, 200 recombinants are found among the A / a and B / b genetic markers. Therefore, the distance that separates them on the chromosome is 20 umg.

Currently, 1 umg (which is 1% recombination) is called cM (centi Morgan). In the above case, the distance between A / a and B / b is 20 cM.

Linkage genetic mapping and its limitations

In a genetic map distances in cM can be added, but obviously recombination percentages cannot be added. You should always map genes that are far enough apart to be able to measure short distances.

If the distance between two markers is very high, the probability that there is a recombination event between them is equal to 1. Therefore, they will always recombine and these genes will behave as if they were independently distributed even though they are linked.

On the other hand, for reasons of various kinds, the maps measured in cM are not linearly related to the amount of DNA involved. Furthermore, the amount of DNA per cM is not universal, and for each particular species it is a particular and average value.

References

1. Botstein, D., White, RL, Skolnick, M., Davis, RW (1980) Construction of a genetic linkage map in man using restriction fragment length polymorphisms. American Journal of Human Genetics, 32: 314-331.
2. Brooker, RJ (2017). Genetics: Analysis and Principles. McGraw-Hill Higher Education, New York, NY, USA.
3. Goodenough, UW (1984) Genetics. WB Saunders Co. Ltd, Pkiladelphia, PA, USA.
4. Griffiths, AJF, Wessler, R., Carroll, SB, Doebley, J. (2015). An Introduction to Genetic Analysis (11 ^th ed.). New York: WH Freeman, New York, NY, USA.
5. Kottler, VA, Schartl, M. (2018) The colorful sex chromosomes of teleost fish. Genes (Basel), doi: 10.3390 / genes9050233.