Linkage disequilibrium of genes

(Thomas Gantt Morgan et al.)

    It is proved that the number of hereditary traits of an organism significantly exceeds the number of chromosomes in the haploid set. For example, the haploid set of the classical object of genetic research, the Drosophila fly, has only four chromosomes, but the number of hereditary traits and, accordingly, the genes that determine them is undoubtedly much greater. This means that each chromosome contains many genes. Therefore, along with traits that are inherited independently, there must be traits that are inherited in conjunction with each other, because they are determined by genes located in the same chromosome. Such genes form a linkage group. The number of linkage groups in organisms of a certain species is equal to the number of chromosomes in the haploid set (for example, in Drosophila 1p=4, in humans 1p=23).

    Experimental studies of the phenomenon of linked inheritance were conducted by the prominent American geneticist T. Morgan and his colleagues. their results substantiated the chromosomal theory of heredity they proposed.

It should be noted that T. Morgan, like G. Mendel in his time, successfully chose the Drosophila fly for research, which later became a classic object for genetic experiments. Drosophila are easy to keep in laboratories, they have significant fertility, rapid generation change (under optimal conditions, a new generation appears every one and a half to two weeks), and a small number of chromosomes, which simplifies observation.

    T. Morgan established the phenomenon of linked inheritance in the following experiment. Drosophila males homozygous for dominant alleles of body color (gray) and wing shape (normal) were crossed with females homozygous for the corresponding recessive alleles (black body - underdeveloped wings). The genotypes of these individuals were designated EEUU and EEUU, respectively. All the hybrids of the first generation had gray bodies and normal wings, i.e., they were heterozygous for both pairs of alleles (genotype - EEUU) (Fig. 1.109).

    The hybrids were then crossed with individuals homozygous for the corresponding recessive alleles (analyzing crosses).

    Theoretically, one could expect two variants of splitting. If the genes that determine the color of the body and the shape of the wings were contained in nonhomologous chromosomes, i.e., inherited independently, the split would be as follows: 25% of individuals with gray bodies and normal wings, 25% with gray bodies and underdeveloped wings, another 25% with black bodies and normal wings, and 25% with black bodies and underdeveloped wings (i.e., in the ratio of 1:1:1:1:1). If these genes were located on the same chromosome and were inherited in a linked fashion, 50% of individuals with gray bodies and normal wings and 50% with black bodies and underdeveloped wings would be obtained (i.e., 1:1).

    In fact, 41.5 % of individuals had a gray body and normal wings, 41.5 % had a black body and underdeveloped wings, 8.5 % had a gray body and underdeveloped wings, and 8.5 % had a black body and normal wings, i.e., the split approached the ratio of phenotypes 1:1 (as in the case of linked inheritance), but at the same time all four variants of the phenotype appeared (as in the case of independent inheritance) Based on these data, T. X. Morgan suggested that the genes that determine the color of the body and the shape of the wings are located in one chromosome, but in the process of meiosis during the formation of gametes, homologous chromosomes can exchange sites, that is, there is a phenomenon called chromosome crossover, or crossover.

    Crossover is the exchange of homologous chromosomes during cell division, mainly in the prophase of the first meiotic division, sometimes in mitosis. The experiments of T. Morgan, C. Bridges, and A. Sturtevant showed that there is no absolutely complete gene crossover, in which genes are always transmitted together. The probability that two genes localized in the same chromosome will not diverge during meiosis ranges from 1 to 0.5. In nature, incomplete linkage prevails due to the crossing of homologous chromosomes and gene recombination.

The cytologic picture of crossover was first described by the Danish scientist F. Janssens.

 Crossover occurs only when the genes are in the heterozygous state (AB/AB). If the genes are in a homozygous state (AB/AB or AB/AB), the exchange of identical sites does not give new combinations of genes in gametes and in a generation. The frequency (percentage) of crossover between genes depends on the distance between them: the further they are located from each other, the more often crossover occurs. T. Morgan proposed to measure the distance between genes as a percentage of crossover using the formula:

N1∕N2 X 100 = % crossover,

where N1 is the total number of individuals in F;

      N2 is the total number of crossover individuals.

    A chromosome segment with a 1% crossover rate is equal to one morganide (a conventional measure of the distance between genes). The crossover frequency is used to determine the relative position of genes and the distance between them. New technologies are used to build a human genetic map. Cytogenetic maps of chromosomes have been constructed.

    There are several types of crossover: double, multiple (complex), irregular, and unequal.

Crossover leads to a new combination of genes that causes a change in phenotype. In addition, along with mutations, it is an important factor in the evolution of organisms.

This evidence was the basis of the chromosomal theory of heredity:

1. Genes are arranged in chromosomes in a linear order along their length; different chromosomes contain different numbers of genes; the set of genes of each non-homologous chromosome is unique.

2. Allelic genes occupy specific and identical loci (places) on homologous chromosomes.

3. Genes located in the same chromosome form a linkage group, due to which some traits are linked together and passed on to the offspring. The number of linkage groups is equal to the haploid set of chromosomes. The linkage is not absolute.

4. During meiosis, which occurs only when gametes are formed, the diploid number of chromosomes is halved (haploid number). This corresponds to the law of cleavage, according to which the genetic material of both parents is combined in different ways in gametes.

5. According to the law of independent distribution, paternal and maternal sets of unlinked genes are split independently of each other. If the unlinked genes are located in different chromosomes, then during meiosis the maternal and paternal chromosomes should be distributed randomly between the gametes.

6. Between the genes of homologous paternal and maternal groups, linkage can occur due to crossover, reciprocal recombination. This corresponds to the formation of chiasms during the conjugation of homologous chromosomes in meiosis (genetic crossover).

7. The strength of adhesion between genes is inversely proportional to the distance between them. The closer the genes are located in one chromosome, the stronger their linkage, the fewer recombinations will occur between them, and vice versa. The distance between genes is measured as a percentage of crossover. One percent of crossover corresponds to one morganide.

8. Each biological species is characterized by a specific set of chromosomes - the karyotype