Causes of hereditary variability. Hereditary variability, its types. Types of mutations, their causes. The role of mutations in the evolution of the organic world and selection. By level of occurrence

He named this type of variability uncertain, since it is initially impossible to determine what changes will appear, in addition, they are always individual.

In each sufficiently long-existing population of individuals, various mutations arise spontaneously and undirectedly, which are subsequently combined more or less randomly with various hereditary properties already existing in the aggregate.

Variability caused by the occurrence of mutations is called mutational, and variability caused by further recombination of genes as a result of crossing is called combinative.

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Combinative variation is variation that occurs due to the recombination of genes during gamete fusion. Main reasons:

independent chromosome segregation during meiosis;
a chance meeting of gametes, and as a result, a combination of chromosomes during fertilization;
recombination of genes due to crossing over.

Mutational variability

Mutational variability is variability caused by the action of mutagens on the body, resulting in mutations (reorganization of the reproductive structures of the cell). Mutagens are physical, chemical and biological.

Mutation theory

The main provisions of the mutation theory in 1901-1903 were developed by Hugo de Vries, and wrote about it in his work The Mutation Theory. This work rejected the then-current understanding of inheritance as the main mechanism of variation in Darwin's theory. Instead, he introduced the term “mutation,” which denoted the unexpected appearance of new characteristics in the phenotype, not caused by heredity. Basic provisions of the theory:

Mutations occur suddenly, spasmodically, as discrete changes in characteristics.
Unlike non-hereditary changes, mutations are qualitative changes that are passed on from generation to generation.
Mutations manifest themselves in different ways and can be both beneficial and harmful, both dominant and recessive.
The probability of detecting mutations depends on the number of individuals examined.
Similar mutations may occur repeatedly.
Mutations are undirected (spontaneous), that is, any part of the chromosome can mutate, causing changes in both minor and vital signs.

Almost any change in the structure or number of chromosomes, in which the cell retains the ability to reproduce itself, causes a hereditary change in the characteristics of the organism. According to the nature of the change in the genome, that is, the set of genes contained in a haploid set of chromosomes, gene, chromosomal and genomic mutations are distinguished.

Role in evolution

The entire variety of individual differences is based on hereditary variability, which includes:

Both sharp qualitative differences, not connected with each other by transitional forms, and purely quantitative differences, forming continuous series in which close members of the series can differ from each other as little as desired;
Both changes in individual characteristics and properties (independent variability), and interrelated changes in a number of characteristics (correlative variability);
Both changes that have adaptive significance (adaptive variability) and changes that are “indifferent” or even reduce the viability of their carriers (non-adaptive variability).

All these types of hereditary changes constitute the material of the evolutionary process (see Microevolution). In the individual development of an organism, the manifestation of hereditary traits and properties is always determined not only by the main genes responsible for these traits and properties, but also by their interaction with many other genes that make up the genotype of the individual, as well as by the environmental conditions in which the development of the organism occurs.

Accuracy in the transmission of genetic information over generations is undeniably important, but excessive conservation of genetic information contained in individual genetic loci can be harmful to the organism and the species as a whole.

The evolutionarily established relationships between the accuracy of the functioning of genetic systems and the frequency of errors that occur during the reproduction of genetic information of individual genetic loci are clearly balanced with each other, and have already been established that in some cases they are regulated. Programmed and random heritable changes in the genome, called mutations, can be accompanied by enormous quantitative and qualitative changes in gene expression.

Variability- the ability of living organisms to acquire new characteristics and properties. Thanks to variability, organisms can adapt to changing environmental conditions.

There are two main forms of variability: hereditary and non-hereditary.

Hereditary, or genotypic, variability- changes in the characteristics of the organism due to changes in the genotype. It, in turn, is divided into combinative and mutational. Combinative variability arises due to the recombination of hereditary material (genes and chromosomes) during gametogenesis and sexual reproduction. Mutational variability arises as a result of changes in the structure of hereditary material.

Non-hereditary, or phenotypic, or modification, variability- changes in the characteristics of the organism that are not due to changes in the genotype.

Mutations

Mutations- these are persistent, sudden changes in the structure of the hereditary material at various levels of its organization, leading to changes in certain characteristics of the organism.

The term “mutation” was introduced into science by De Vries. Created by him mutation theory, the main provisions of which have not lost their significance to this day.

Mutations arise suddenly, spasmodically, without any transitions.
Mutations are hereditary, i.e. are persistently passed on from generation to generation.
Mutations do not form continuous series, are not grouped around an average type (as with modification variability), they are qualitative changes.
Mutations are non-directional - any locus can mutate, causing changes in both minor and vital signs in any direction.
The same mutations can occur repeatedly.
Mutations are individual, that is, they occur in individual individuals.

The process of mutation occurrence is called mutagenesis, and environmental factors causing mutations are mutagens.

According to the type of cells in which the mutations occurred, they are distinguished: generative and somatic mutations.

Generative mutations arise in germ cells, do not affect the characteristics of a given organism, and appear only in the next generation.

Somatic mutations arise in somatic cells, manifest themselves in a given organism and are not transmitted to offspring during sexual reproduction. Somatic mutations can be preserved only through asexual reproduction (primarily vegetative).

According to their adaptive value, they are divided into: beneficial, harmful (lethal, semi-lethal) and neutral mutations. Useful- increase vitality, lethal- cause death semi-lethal- reduce vitality, neutral- do not affect the viability of individuals. It should be noted that the same mutation can be beneficial in some conditions and harmful in others.

According to the nature of their manifestation, mutations can be dominant And recessive. If a dominant mutation is harmful, then it can cause the death of its owner in the early stages of ontogenesis. Recessive mutations do not appear in heterozygotes, therefore they remain in the population for a long time in a “hidden” state and form a reserve of hereditary variability. When environmental conditions change, carriers of such mutations may gain an advantage in the struggle for existence.

Depending on whether the mutagen that caused this mutation has been identified or not, they distinguish induced And spontaneous mutations. Typically, spontaneous mutations occur naturally, while induced mutations are caused artificially.

Depending on the level of hereditary material at which the mutation occurred, gene, chromosomal and genomic mutations are distinguished.

Gene mutations

Gene mutations- changes in gene structure. Since a gene is a section of a DNA molecule, a gene mutation represents changes in the nucleotide composition of this section. Gene mutations can occur as a result of: 1) replacement of one or more nucleotides with others; 2) nucleotide insertions; 3) loss of nucleotides; 4) doubling of nucleotides; 5) changes in the order of alternation of nucleotides. These mutations lead to changes in the amino acid composition of the polypeptide chain and, consequently, to changes in the functional activity of the protein molecule. Gene mutations result in multiple alleles of the same gene.

Diseases caused by gene mutations are called genetic diseases (phenylketonuria, sickle cell anemia, hemophilia, etc.). The inheritance of gene diseases obeys Mendel's laws.

Chromosomal mutations

These are changes in the structure of chromosomes. Rearrangements can occur both within one chromosome - intrachromosomal mutations (deletion, inversion, duplication, insertion), and between chromosomes - interchromosomal mutations (translocation).

Deletion— loss of a chromosome section (2); inversion— rotation of a chromosome section by 180° (4, 5); duplication- doubling of the same chromosome section (3); insertion— rearrangement of the area (6).

Chromosomal mutations: 1 - parachromosomes; 2 - deletion; 3 - duplication; 4, 5 — inversion; 6 - insertion.

Translocation- transfer of a section of one chromosome or an entire chromosome to another chromosome.

Diseases caused by chromosomal mutations are classified as chromosomal diseases. Such diseases include “cry of the cat” syndrome (46, 5p -), translocation variant of Down syndrome (46, 21 t21 21), etc.

Genomic mutation called a change in the number of chromosomes. Genomic mutations occur as a result of disruption of the normal course of mitosis or meiosis.

Haploidy- reduction in the number of complete haploid sets of chromosomes.

Polyploidy— increase in the number of complete haploid sets of chromosomes: triploids (3 n), tetraploids (4 n) etc.

Heteroploidy (aneuploidy) - a multiple increase or decrease in the number of chromosomes. Most often, there is a decrease or increase in the number of chromosomes by one (less often two or more).

The most likely cause of heteroploidy is the nondisjunction of any pair of homologous chromosomes during meiosis in one of the parents. In this case, one of the resulting gametes contains one less chromosome, and the other contains one more. The fusion of such gametes with a normal haploid gamete during fertilization leads to the formation of a zygote with a smaller or larger number of chromosomes compared to the diploid set characteristic of a given species: nullosomia (2n - 2), monosomy (2n - 1), trisomy (2n + 1), tetrasomy (2n+ 2) etc.

The genetic diagrams below show that the birth of a child with Klinefelter syndrome or Turner-Shereshevsky syndrome can be explained by the nondisjunction of sex chromosomes during anaphase 1 of meiosis in the mother or father.

1) Nondisjunction of sex chromosomes during meiosis in the mother

R	♀46,XX		×	♂46,XY
Types of gametes	24, XX 24, 0			23, X 23, Y
F	47, XXX trisomy on the X chromosome	47, XXY syndrome Klinefelter		45, X0 Turner syndrome- Shereshevsky	45, Y0 death zygotes

2) Nondisjunction of sex chromosomes during meiosis in the father

R	♀46,XX	×	♂46,XY
Types of gametes	23, X		24, XY 22, 0
F	47, XXY syndrome Klinefelter		45, X0 Turner syndrome- Shereshevsky

Diseases caused by genomic mutations also fall into the chromosomal category. Their inheritance does not obey Mendel's laws. In addition to the above-mentioned Klinefelter or Turner-Shereshevsky syndromes, such diseases include Down syndrome (47, +21), Edwards syndrome (+18), Patau syndrome (47, +15).

Polyploidy characteristic of plants. The production of polyploids is widely used in plant breeding.

The law of homological series of hereditary variability N.I. Vavilova

“Species and genera that are genetically close are characterized by similar series of hereditary variability with such regularity that, knowing the series of forms within one species, one can predict the presence of parallel forms in other species and genera. The closer the genera and species are genetically located in the general system, the more complete the similarity in the series of their variability. Whole families of plants are generally characterized by a certain cycle of variation passing through all the genera and species that make up the family.”

This law can be illustrated by the example of the Poa family, which includes wheat, rye, barley, oats, millet, etc. Thus, the black color of the caryopsis is found in rye, wheat, barley, corn and other plants, and the elongated shape of the caryopsis is found in all studied species of the family. The law of homological series in hereditary variability allowed N.I. himself. Vavilov to find a number of forms of rye, previously unknown, based on the presence of these characteristics in wheat. These include: awned and awnless ears, grains of red, white, black and purple color, mealy and glassy grains, etc.

Hereditary variation of traits *			Rye	Wheat	Barley	Oats	Millet	Sorghum	Corn	Rice	Wheatgrass
Corn	Coloring	Black	+	+	+	—	—	+	+	+	+
	Coloring	Purple	+	+	+	—	—	+	+	+	—
	Form	Round	+	+	+	+	+	+	+	+	+
	Form	Extended	+	+	+	+	+	+	+	+	+
Biol. signs	Lifestyle	Winter crops	+	+	+	+				+
Biol. signs	Lifestyle	Spring	+	+	+	+	+	+	+	+

* Note. The “+” sign means the presence of hereditary forms that have the specified trait.

Open N.I. Vavilov’s law is valid not only for plants, but also for animals. Thus, albinism occurs not only in different groups of mammals, but also in birds and other animals. Short toedness is observed in humans, cattle, sheep, dogs, birds, the absence of feathers in birds, scales in fish, wool in mammals, etc.

The law of homological series of hereditary variability is of great importance for selection, since it allows us to predict the presence of forms not found in a given species, but characteristic of closely related species. Moreover, the desired form can be found in the wild or obtained through artificial mutagenesis.

Artificial mutations

Spontaneous mutagenesis constantly occurs in nature, but spontaneous mutations are a fairly rare occurrence, for example, in Drosophila, the white eye mutation is formed with a frequency of 1:100,000 gametes.

Factors whose impact on the body leads to the appearance of mutations are called mutagens. Mutagens are usually divided into three groups. Physical and chemical mutagens are used to artificially produce mutations.

Induced mutagenesis is of great importance because it makes it possible to create valuable starting material for breeding, and also reveals ways to create means of protecting humans from the action of mutagenic factors.

Modification variability

Modification variability- these are changes in the characteristics of organisms that are not caused by changes in the genotype and arise under the influence of environmental factors. The habitat plays a big role in the formation of the characteristics of organisms. Each organism develops and lives in a certain environment, experiencing the action of its factors that can change the morphological and physiological properties of organisms, i.e. their phenotype.

An example of the variability of characteristics under the influence of environmental factors is the different shape of the leaves of the arrowhead: leaves immersed in water have a ribbon-like shape, leaves floating on the surface of the water are round, and those in the air are arrow-shaped. Under the influence of ultraviolet rays, people (if they are not albinos) develop a tan as a result of the accumulation of melanin in the skin, and the intensity of the skin color varies from person to person.

Modification variability is characterized by the following main properties: 1) non-heritability; 2) the group nature of the changes (individuals of the same species placed in the same conditions acquire similar characteristics); 3) correspondence of changes to the influence of environmental factors; 4) dependence of the limits of variability on the genotype.

Despite the fact that signs may change under the influence of environmental conditions, this variability is not unlimited. This is explained by the fact that the genotype determines specific boundaries within which changes in a trait can occur. The degree of variation of a trait, or the limits of modification variability, is called reaction norm. The reaction norm is expressed in the totality of phenotypes of organisms formed on the basis of a certain genotype under the influence of various environmental factors. As a rule, quantitative traits (plant height, yield, leaf size, milk yield of cows, egg production of chickens) have a wider reaction rate, that is, they can vary widely than qualitative traits (coat color, milk fat content, flower structure, blood type) . Knowledge of reaction norms is of great importance for agricultural practice.

Modification variability of many characteristics of plants, animals and humans obeys general laws. These patterns are identified based on the analysis of the manifestation of the trait in a group of individuals ( n). The degree of expression of the studied trait among members of the sample population is different. Each specific value of the characteristic being studied is called option and denoted by the letter v. The frequency of occurrence of individual variants is indicated by the letter p. When studying the variability of a trait in a sample population, a variation series is compiled in which individuals are arranged in ascending order of the indicator of the trait being studied.

For example, if you take 100 ears of wheat ( n= 100), count the number of spikelets in an ear ( v) and the number of ears with a given number of spikelets, then the variation series will look like this.

Variant ( v)	14	15	16	17	18	19	20
Frequency of occurrence ( p)	2	7	22	32	24	8	5

Based on the variation series, it is constructed variation curve— graphical display of the frequency of occurrence of each option.

The average value of a characteristic is more common, and variations significantly different from it are less common. It is called "normal distribution". The curve on the graph is usually symmetrical.

The average value of the characteristic is calculated using the formula:

Where M— average value of the characteristic; ∑( v

Hereditary variability

Hereditary or genotypic variability - variability due to changes in the genotype; it happens: combinative- arising as a result of recombination of hereditary material during the process of meiosis and fusion of gametes; mutational leading to changes in genetic material.

As a result of crossing over in prophase-1 of meiosis, in anaphase-1 of meiosis - as a result of the divergence to the poles of haploid sets of chromosomes, in each of which the number of paternal and maternal ones can be different, and in anaphase-2, when the chromatids that differ as a result of crossing over diverge. And when unique gametes merge, unique combinations of gene alleles are formed in each genotype, which come under the control of selection.

Mutational variability. The term “mutation” was first introduced into science by the Dutch geneticist G. de Vries. While conducting experiments with evening primrose (an ornamental plant), he accidentally discovered specimens that differed in a number of characteristics from the rest (large growth, smooth, narrow and long leaves, red veins of the leaves and a wide red stripe on the calyx of the flower, etc.). Moreover, during seed propagation, plants persistently retained these characteristics from generation to generation. As a result of generalizing his observations, de Vries created a mutation theory, the main provisions of which have not lost their meaning to this day: Mutations arise suddenly, spasmodically, without any transitions; mutations are hereditary, i.e. persistently passed on from generation to generation; mutations do not form continuous series, are not grouped around an average type (as with modification variability), they are qualitative changes. Mutations are not directed - any locus can mutate, causing changes in both minor and vital signs in any direction; the same mutations can occur repeatedly; mutations are individual, that is, they occur in individual individuals.

The process of occurrence of mutations is called mutagenesis, organisms in which mutations have occurred are called mutants, and environmental factors causing the appearance of mutations are called mutagens. There are several classifications of mutations:

Mutations according to the place of their occurrence: generative - occurring in germ cells. They do not affect the characteristics of a given organism, but appear only in the next generation. Somatic - arising in somatic cells. These mutations appear in this organism and are not transmitted to offspring during sexual reproduction (a black spot against the background of brown wool in astrakhan sheep). Somatic mutations can be preserved only through asexual reproduction (primarily vegetative).

Mutations according to adaptive value: beneficial - increasing the viability of individuals, more often harmful - decreasing, and neutral - not affecting the viability of individuals. This classification is very conditional, since the same mutation can be beneficial in some conditions and harmful in others.

Mutations according to the nature of their manifestation: dominant - appear in the first generation and come under the control of selection; and recessive (mutations that do not appear in heterozygotes, therefore they persist for a long time in the population and form a reserve of hereditary variability). Most mutations are recessive.

Mutations that change the state of a gene: direct - a transition of a gene from a wild type to a new state, reverse - a transition of a gene from a mutant state to a wild type. Mutations according to the nature of their occurrence: spontaneous - mutations that arose naturally under the influence of environmental factors, induced - mutations artificially caused by the action of mutagenic factors.

Mutations by the nature of the genotype change: gene, chromosomal, genomic. Mutations can cause various changes in the genotype, affecting individual genes, entire chromosomes, or the entire genome.

Genomic mutations are called mutations that result in a change in the number of chromosomes in a cell. Genomic mutations arise as a result of disturbances in mitosis or meiosis, leading either to uneven divergence of chromosomes to the poles of the cell, or to doubling of chromosomes, but without division of the cytoplasm. Depending on the nature of the change in the number of chromosomes, they distinguish: polyploidy - an increase in the number of chromosomes, a multiple of the genome. Polyploidy is more often observed in protozoa and plants. Depending on the number of haploid sets of chromosomes contained in cells, they are distinguished: triploids (3n), tetraploids (4n), etc. They can be: autopolyploids - polyploids resulting from the multiplication of genomes of one species, allopolyploids - polyploids resulting from the multiplication of genomes of different species (typical of interspecific hybrids).

Heteroploidy (aneuploidy)- an increase or decrease in the number of chromosomes that is not multiple to the genome. Most often, there is a decrease or increase in the number of chromosomes by one (less often two or more). Due to the nondisjunction of any pair of homologous chromosomes in meiosis, one of the resulting gametes contains one less chromosome, and the other one more. The fusion of such gametes with a normal haploid gamete during fertilization leads to the formation of a zygote with a smaller or larger number of chromosomes compared to the diploid set characteristic of a given species. Among aneuploids there are: trisomics - organisms with a set of chromosomes 2n + 1, monosomics - organisms with a set of chromosomes 2n -1. For example, Down syndrome in humans occurs as a result of trisomy on the 21st pair of chromosomes.

Chromosomal mutations - mutations that cause changes in the structure of chromosomes. Rearrangements can occur both within one chromosome - intrachromosomal mutations, and between non-homologous chromosomes - interchromosomal mutations.

Intrachromosomal mutations: deletion - loss of part of a chromosome (АВСD ® AB); inversion - rotation of a chromosome section by 180˚ (ABCD ® ACBD); duplication - doubling of the same chromosome section; (ABCD ® ABCBCD);

Interchromosomal mutations: translocation - transfer of a section of one chromosome to another, non-homologous to it (ABCD ® ABCD1234). It is possible to combine two non-homologous chromosomes into one chromosome.

Gene mutations are changes in the structure of a DNA molecule in a section of a specific gene that encodes the structure of a specific protein molecule. These mutations entail a change in the structure of proteins, that is, a new amino acid sequence appears in the polypeptide chain, resulting in a change in the functional activity of the protein molecule.

Thanks to gene mutations, a series of multiple alleles of the same gene occurs. Most often, gene mutations occur as a result of the replacement of one or more nucleotides with others, insertion of nucleotides, loss of nucleotides, or changes in the order of alternation of nucleotides.

Spontaneous mutagenesis occurs constantly in nature. However, spontaneous mutations are rare. For example, in humans and other multicellular organisms it is also 10 -5 per gene per gamete per generation. In other words, only in one out of 100 thousand gametes the gene is changed. But there are a lot of genes in each gamete. According to modern estimates, the human genome contains about 30 thousand genes. Consequently, in each generation, about a third of human gametes carry new mutations in some gene.

1. What is heredity?

Answer. Heredity is the property of organisms to repeat similar types of metabolism and individual development in general over a number of generations. It is ensured by self-reproduction of material units of heredity - genes localized in specific structures of the cell nucleus (chromosomes) and cytoplasm. Together with variability, heredity ensures the constancy and diversity of life forms and underlies the evolution of living nature.

2. What is variability?

Answer. Variability is a variety of characters and properties in individuals and groups of individuals of any degree of kinship. Variability is inherent in all living organisms. Variability is distinguished: hereditary. and non-hereditary. ;individual and group. Hereditary variability is caused by the occurrence of mutations, non-hereditary variability is caused by the influence of environmental factors. The phenomena of heredity and variability underlie evolution.

Questions after § 46

1. What types of variability do you know?

Answer. There are two types of variability: modification (phenotypic) and hereditary (genotypic).

Changes in the characteristics of an organism that do not affect its genes and cannot be transmitted to subsequent generations are called modification, and this type of variability is called modification.

The following main characteristics of modification variability can be listed:

– modification changes are not passed on to descendants;

– modification changes occur in many individuals of the species and depend on environmental influences;

– modification changes are possible only within the limits of the reaction norm, i.e. they are ultimately determined by the genotype

Hereditary variability is caused by changes in the genetic material and is the basis of the diversity of living organisms, as well as the main reason for the evolutionary process, since it supplies material for natural selection.

The occurrence of changes in the hereditary material, i.e., in DNA molecules, is called mutational variability. Moreover, changes can occur both in individual molecules (chromosomes) and in the number of these molecules. Mutations occur under the influence of various external and internal environmental factors.

2. What are the main signs of modification variability?

Answer. Most often, quantitative traits are subject to modification - height, weight, fertility, etc. A classic example of modification variability is the variability of leaf shape in the arrowhead plant, which takes root under water. One individual arrowhead has three types of leaves, depending on where the leaf develops: underwater, on the surface or in the air. These differences in leaf shape are determined by the degree of illumination, and the set of genes in the cells of each leaf is the same.

Various signs and properties of an organism are characterized by greater or lesser dependence on environmental conditions. For example, in humans, the color of the iris and blood type are determined only by the corresponding genes, and living conditions cannot influence these signs. But height, weight, and physical endurance strongly depend on external conditions, for example, on the quality of nutrition, physical activity, etc.

3. What is the reaction norm?

Answer. The limits of modification variability of any trait are called the reaction norm. The reaction rate is determined genetically and is inherited.

The variability of a sign is sometimes very large, but it cannot go beyond the limits of the reaction norm. For some traits, the reaction norm is very wide (for example, the shearing of wool from sheep, the milk production of cows), while other traits are characterized by a narrow reaction norm (coat color in rabbits).

A very important conclusion follows from the above. It is not the trait itself that is inherited, but the ability to manifest this trait under certain conditions, in other words, the norm of the body’s reaction to external conditions is inherited

4. What forms of hereditary variability do you know?

Answer. Hereditary variability manifests itself in two forms - combinative and mutational.

Mutational variability is changes in the DNA of a cell (changes in the structure and number of chromosomes). Occur under the influence of ultraviolet radiation, radiation (X-rays), etc. They are inherited and serve as material for natural selection (the mutation process is one of the driving forces of evolution).

Combinative variability occurs when the genes of the father and mother are recombined (mixed). Sources:

1) Crossing over during meiosis (homologous chromosomes come close together and change sections).

2) Independent chromosome segregation during meiosis.

3) Random fusion of gametes during fertilization.

5. What are the causes of combinational variability?

Answer. The basis of combinative variability is the sexual process, as a result of which a huge set of diverse genotypes arises.

Let's look at the example of a person. Each person's cells contain 23 maternal and 23 paternal chromosomes. When gametes are formed, only 23 chromosomes will end up in each of them, and how many of them will be from the father and how many from the mother is a matter of chance. This is where the first source of combinative variability lies.

Its second reason is crossing over. Not only does each of our cells carry the chromosomes of our grandparents, but a certain part of these chromosomes received, as a result of crossing over, part of their genes from homologous chromosomes that previously belonged to another line of ancestors. Such chromosomes are called recombinant. Participating in the formation of a new generation organism, they lead to unexpected combinations of characteristics that were not present in either the paternal or maternal organism.

Finally, the third reason for combinative variability is the random nature of meetings of certain gametes during the process of fertilization.

All three processes underlying combinative variability act independently of each other, creating a huge variety of all possible genotypes.