Gene interaction

         The genotype includes a large number of genes that function and interact as an integrated system. In his experiments, G. Mendel discovered only one form of interaction between allelic genes - complete dominance of one allele and complete recessiveness of another. The genotype of an organism cannot be considered as a simple sum of independent genes, each of which functions independently of the others. The phsnotypic manifestation of a particular trait is the result of the interaction of many genes.

       There are two main groups of gene interactions: the interaction between allelic genes and the interaction between non-allelic genes. However, it should be understood that this is not a physical interaction of the genes themselves, but the interaction of primary and secondary products that will determine a particular trait. In the cytoplasm, there is an interaction between proteins - enzymes, the synthesis of which is determined by genes, or between substances that are formed under the influence of these enzymes.

      The following types of interaction are possible:

1) the formation of a certain trait requires the interaction of two enzymes whose synthesis is determined by two non-allelic genes;

2) an enzyme synthesized with the participation of one gene completely inhibits or inactivates the action of an enzyme produced by another non-allelic gene

3) two enzymes, the formation of which is controlled by two non-allelic genes, affect one trait or one process so that their combined action leads to the emergence and intensification of the trait.

       Interaction of allelic genes. Genes that occupy identical (homologous) loci on homologous chromosomes are called allelic. Each organism has only two allelic genes.

The following forms of interaction between allelic genes are known: complete dominance, incomplete dominance, codominance, and overdominance.

       The main form of interaction is complete dominance, which was first described by G. Mendel. Its essence lies in the fact that in a heterozygous organism, the manifestation of one of the alleles dominates the manifestation of the other. In case of complete dominance, a 1:2:1 genotype split does not coincide with a 3:1 phenotype split. In medical practice, out of two thousand monogenic hereditary diseases, almost half of them are characterized by the dominance of pathological genes over normal ones. In heterozygotes, the pathological allele is manifested in most cases by signs of the disease (dominant phenotype).

         Incomplete dominance is a form of interaction when in a heterozygous organism (Aa) the dominant gene (A) does not completely suppress the recessive gene (a), resulting in the manifestation of an intermediate trait between the parents. In this case, the split between genotype and phenotype coincides and is 1:2:1 

         When codominating in heterozygous organisms, each of the allelic genes causes the formation of a product dependent on it, i.e., the products of both alleles are detected. A classic example of such a manifestation is the blood group system, in particular the ABO system, when human red blood cells carry antigens on the surface controlled by both alleles, this form of manifestation is called codominance. 

       Overdominance - when the dominant gene in the heterozygous state is stronger than in the homozygous state. For example, in Drosophila with the genotype AA - normal life expectancy; Aa - extended life expectancy; aa - fatal outcome

Multiple allelicism

        Each organism has only two allelic genes. However, in nature, the number of alleles can often be more than two, when a locus can be in different states. In such cases, we speak of multiple alleles or multiple allomorphism.

        Multiple alleles are denoted by one letter with different indices, for example: A, A1, A3... Allelic genes are localized in the same parts of homologous chromosomes. Since there are always two homologous chromosomes in the karyotype, even with multiple alleles, each organism can have only two identical or different alleles at the same time. Only one of them enters the germ cell (along with the difference in homologous chromosomes).  Multiple alleles are characterized by the influence of all alleles on the same trait. The only difference between them is the degree of development of the trait.

        The second feature is that somatic cells or cells of diploid organisms contain a maximum of two alleles out of several, since they are located in the same chromosome locus. Another feature is inherent in multiple alleles. According to the nature of dominance, allomorphic traits are placed in a sequential row: more often a normal, unchanged trait dominates over others; the second gene in the row is recessive to the first, but dominates over the following, etc. One example of the manifestation of multiple alleles in humans is the ABO blood groups. Multiple allelicism is important biologically and practically because it enhances combinatorial variation, especially genotypic variation.

Interaction of non-allelic genes

     There are many cases where a trait or property is determined by two or more non-allelic genes that interact with each other. However, here, too, the interaction is conditional, since it is not the genes that interact, but the products they control. In this case, there is a deviation from the Mendelian patterns of cleavage.

There are four main types of gene interactions: complementarity, epistasis, polymerization, and modifying effects (pleiotropy).

      Complementarity is a type of interaction between non-allelic genes when one dominant gene complements the action of another non-allelic dominant gene, and together they determine a new trait that is absent in the parents. Moreover, the corresponding trait develops only in the presence of both non-allelic genes. For example, the gray color of the coat in mice is controlled by two genes (A and B). The A gene determines the synthesis of pigment, but both homozygotes (AA) and heterozygotes (AA) are albinos. Another gene, B, ensures the accumulation of pigment mainly at the base and tips of the hair. Crossing of diheterozygotes (AaB x AaB) leads to a 9:3:4 split of hybrids. Numerical ratios in complementary interaction can be 9:7; 9:6:1 (modification of Mendelian cleavage).

      An example of complementary interaction of genes in humans is the synthesis of the protective protein interferon. Its formation in the body is associated with the complementary interaction of two non-allelic genes located in different chromosomes.

      Epistasis is the interaction of non-allelic genes in which one gene suppresses the action of another non-allelic gene. Both dominant and recessive genes can cause suppression (A>B, a>B, B>A, B>A), and depending on this, epistasis is distinguished between dominant and recessive. A suppressive gene is called an inhibitor or suppressor. Inhibitor genes generally do not determine the development of a particular trait, but only suppress the effect of another gene.

A gene whose effect is suppressed is called a hypostatic gene. With epistatic gene interaction, the split by phenotype in F2 is 13:3, 12:3:1, or 9:3:4, etc. The color of pumpkin fruits and the color of horses are determined by this type of interaction.

        If the suppressor gene is recessive, then cryptomeria occurs (from the Greek chrysalis - secret, hidden). In humans, the "Bombay phenomenon" is an example of this. In this case, the rare recessive allele "x" in the homozygous state (xx) suppresses the activity of the jB gene (which determines the B (III) blood group of the ABO system). Therefore, a woman with the genotype jb_xx phenotypically has blood group 0 (I).

  Polygenic inheritance of quantitative traits

   - pleiotropy

   - expression and penetrance of genes

    Most quantitative traits of organisms are determined by several non-allelic genes (polygenes). The interaction of such genes in the process of trait formation is called polymerase chain reaction. In this case, two or more dominant alleles equally affect the development of the same trait. Therefore, polymeric genes are usually designated by a single letter of the Latin alphabet with a numerical index, for example: A1A1 and a1a1. For the first time, unambiguous factors were identified by the Swedish geneticist Nilsson-Ele (1908) when studying the inheritance of color in wheat. It was found that this trait depends on two polymerase genes, so when crossing dominant and recessive digomozygotes - colored (A1A1, A2 A2) with colorless (a1a1, a2a2) - in F, all plants produce colored seeds, although they are noticeably lighter than parental specimens that have red seeds. In F, when individuals of the first generation are crossed, a phenotype split is detected in a ratio of 15 : 1, because only recessive digomozygotes (aLa1 a2a2.) are colorless. In pigmented specimens, the color intensity varies greatly depending on the number of dominant alleles they have received: it is maximum in dominant digomozygotes (A1A1 A2 A2 and minimum in carriers of one of the dominant alleles).

        An important feature of polymery is the summation of the effect of non-allelic genes on the development of quantitative traits. While in monogenic inheritance of a trait, there are three possible variants of gene doses in the genotype: AA, Aa, aa, then in polygenic inheritance the number of them increases to four or more. The summation of polymerase gene "doses" ensures the existence of a continuous series of quantitative changes.

         The biological significance of polymerization is also that the traits encoded by these genes are more stable than those encoded by a single gene. An organism without polymeric genes would be very unstable: any mutation or recombination would lead to sharp variability, and this is unfavorable in most cases.

        Animals and plants have many polygenic traits, including those that are valuable to the economy: growth rate, early maturity, egg production, milk production, sugar and vitamin content, etc.  Skin pigmentation in humans is determined by five or six polymerase genes. In the indigenous people of Africa (Negroid race), dominant alleles prevail, while in the Caucasian race, recessive alleles prevail. That is why mulattoes have intermediate pigmentation, but in mulatto marriages, they may have both more and less intensely pigmented children.

Many morphological, physiological, and pathological features of humans are determined by polymerase genes: height, body weight, blood pressure, etc. The development of such traits in humans is subject to the general laws of polygenic inheritance and depends on environmental conditions. In these cases, there is, for example, a predisposition to hypertension, obesity, etc. Under favorable environmental conditions, these traits may not manifest themselves or manifest themselves to a lesser extent. This is how polygenic traits differ from monogenic traits. By changing environmental conditions, it is possible to largely prevent a number of polygenic diseases.

 Pleiotropy.

        The pleiotropic effect of genes is the dependence of several traits on one gene, that is, the multiple effects of one gene. In Drosophila, the gene for white eyes simultaneously affects body color, wing length, and the structure of the reproductive apparatus, reduces fertility, and shortens life expectancy. In humans, there is a well-known hereditary disease called arachnodactyly ("spider fingers" - very thin and long fingers), or Marfan's disease. The gene responsible for this disease causes disorders in the development of connective tissue and simultaneously affects the development of several features: disorders of the eye lens, abnormalities in the cardiovascular system. 

        The pleiotropic effect of a gene can be primary and secondary. In primary pleiotropy, a gene has a multiple effect. For example, in Hartnup disease, a gene mutation leads to impaired absorption of the amino acid tryptophan in the intestines and its reabsorption in the renal tubules. In this case, the membranes of intestinal epithelial cells and renal tubules are simultaneously affected with disorders of the digestive and excretory systems. In secondary pleiotropy, there is one primary phenotypic manifestation of the gene, followed by a stepwise process of secondary changes that lead to multiple effects. For example, in sickle cell disease, homozygotes show several pathological signs: anemia, enlarged spleen, skin, heart, kidney, and brain lesions. Therefore, homozygotes for the sickle cell gene usually die in childhood. All of these phenotypic manifestations of the gene constitute a hierarchy of secondary manifestations. The primary cause, the direct phenotypic manifestation of the defective gene, is abnormal hemoglobin and sickle-shaped red blood cells. As a result, other pathological processes occur sequentially: clumping and destruction of red blood cells, anemia, defects in the kidneys, heart, and brain These pathological signs are secondary. In pleiotropy, a gene, affecting one primary trait, can also change or modify the expression of other genes, and therefore the concept of modifier genes was introduced. The latter enhance or weaken the development of traits encoded by the "main" gene.  The indicators of the dependence of the functioning of hereditary traits on the characteristics of the genotype are penetrance and expressivity.

      When considering the effect of genes and their alleles, it is necessary to take into account the modifying influence of the environment in which the organism develops. If primrose plants are crossed at a temperature of 15-20 °C, then in F1, according to the Mendelian scheme, the entire generation will have pink flowers. But when such a cross is carried out at a temperature of 35 °C, all hybrids will have white flowers. If you cross at a temperature of about 30 °C, you get a different ratio (from 3:1 to 100 percent) of plants with white flowers.

      This fluctuation of classes during splitting, depending on environmental conditions, is called penetrance - the strength of phenotypic manifestation. Thus, penetrance is the frequency of gene expression, the phenomenon of the appearance or absence of a trait in organisms of the same genotype.

        Penetrance varies significantly among both dominant and recessive genes. Along with genes whose phenotype appears only under a combination of certain conditions and rather rare external conditions (high penetrance), humans have genes whose phsnotypic manifestation occurs under any combination of external conditions (low penetrance). Penetrance is measured by the percentage of organisms with a phenotypic trait out of the total number of carriers of the corresponding allele examined.

       If a gene completely determines the phenotypic manifestation, regardless of the environment, it has a penetrance of 100 percent. However, some dominant genes are less regular. For example, polydactyly has a clear vertical inheritance, but there are generational gaps. The dominant abnormality, precocious puberty, is characteristic of males only, but sometimes the disease can be transmitted from a man who has not suffered from this pathology. The penetrance rate shows what percentage of gene carriers manifest the corresponding phenotype. So, penetrance depends on the genes, on the environment, on both. Thus, it is not a constant property of a gene, but a function of genes in certain environmental conditions.

     Expression is a change in the quantitative manifestation of a trait in different individuals carrying the corresponding allele.

     In dominant hereditary diseases, expression can vary. In one and the same family, hereditary diseases can manifest themselves in a range from mild, barely noticeable to severe: various forms of hypertension, schizophrenia, diabetes, etc. Recessive hereditary diseases within a family manifest themselves in the same way and have slight fluctuations in expression.