The genetic code is a specific sequence. The concept of a gene, genetic code

They line up in chains and thus produce sequences of genetic letters.

Genetic code

The proteins of almost all living organisms are built from only 20 types of amino acids. These amino acids are called canonical. Each protein is a chain or several chains of amino acids connected in a strictly defined sequence. This sequence determines the structure of the protein, and therefore all its biological properties.

CUU (Leu/L)Leucine
CUC (Leu/L)Leucine
CUA (Leu/L)Leucine
CUG (Leu/L)Leucine

In some proteins, nonstandard amino acids, such as selenocysteine and pyrrolysine, are inserted by a ribosome reading the stop codon, depending on the sequences in the mRNA. Selenocysteine is now considered to be the 21st, and pyrrolysine the 22nd, amino acids that make up proteins.

Despite these exceptions, all living organisms have common genetic codes: a codon consists of three nucleotides, where the first two are decisive; codons are translated by tRNA and ribosomes into an amino acid sequence.

Deviations from the standard genetic code.

Example	Codon	Normal meaning	Reads like:
Some types of yeast Candida	C.U.G.	Leucine	Serin
Mitochondria, in particular in Saccharomyces cerevisiae	CU(U, C, A, G)	Leucine	Serin
Mitochondria of higher plants	CGG	Arginine	Tryptophan
Mitochondria (in all studied organisms without exception)	U.G.A.	Stop	Tryptophan
Mitochondria in mammals, Drosophila, S. cerevisiae and many protozoa	AUA	Isoleucine	Methionine = Start
Prokaryotes	G.U.G.	Valin	Start
Eukaryotes (rare)	C.U.G.	Leucine	Start
Eukaryotes (rare)	G.U.G.	Valin	Start
Prokaryotes (rare)	UUG	Leucine	Start
Eukaryotes (rare)	A.C.G.	Threonine	Start
Mammalian mitochondria	AGC, AGU	Serin	Stop
Drosophila mitochondria	A.G.A.	Arginine	Stop
Mammalian mitochondria	AG(A, G)	Arginine	Stop

History of ideas about the genetic code

However, in the early 60s of the 20th century, new data revealed the inconsistency of the “code without commas” hypothesis. Then experiments showed that codons, considered meaningless by Crick, could provoke protein synthesis in vitro, and by 1965 the meaning of all 64 triplets was established. It turned out that some codons are simply redundant, that is, a whole series of amino acids are encoded by two, four or even six triplets.

Notes

Genetic code supports targeted insertion of two amino acids by one codon. Turanov AA, Lobanov AV, Fomenko DE, Morrison HG, Sogin ML, Klobutcher LA, Hatfield DL, Gladyshev VN. Science. 2009 Jan 9;323(5911):259-61.
The AUG codon encodes methionine, but at the same time serves as a start codon - translation usually begins with the first AUG codon of mRNA.
NCBI: "The Genetic Codes", Compiled by Andrzej (Anjay) Elzanowski and Jim Ostell
Jukes TH, Osawa S, The genetic code in mitochondria and chloroplasts., Experience. 1990 Dec 1;46(11-12):1117-26.
Osawa S, Jukes TH, Watanabe K, Muto A (March 1992). "Recent evidence for evolution of the genetic code." Microbiol. Rev. 56 (1): 229–64. PMID 1579111.
SANGER F. (1952). "The arrangement of amino acids in proteins." Adv Protein Chem. 7 : 1-67. PMID 14933251.
M. Ichas Biological code. - World, 1971.
WATSON JD, CRICK FH. (April 1953). “Molecular structure of nucleic acids; a structure for deoxyribose nucleic acid." Nature 171 : 737-738. PMID 13054692.
WATSON JD, CRICK FH. (May 1953). "Genetic implications of the structure of deoxyribonucleic acid." Nature 171 : 964-967. PMID 13063483.
Crick FH. (April 1966). “The genetic code - yesterday, today, and tomorrow.” Cold Spring Harb Symp Quant Biol.: 1-9. PMID 5237190.
G. GAMOW (February 1954). "Possible Relation between Deoxyribonucleic Acid and Protein Structures." Nature 173 : 318. DOI:10.1038/173318a0. PMID 13882203.
GAMOW G, RICH A, YCAS M. (1956). "The problem of information transfer from the nucleic acids to proteins." Adv Biol Med Phys. 4 : 23-68. PMID 13354508.
Gamow G, Ycas M. (1955). “STATISTICAL CORRELATION OF PROTEIN AND RIBONUCLEIC ACID COMPOSITION. " Proc Natl Acad Sci U S A. 41 : 1011-1019. PMID 16589789.
Crick FH, Griffith JS, Orgel LE. (1957). “CODES WITHOUT COMMAS. " Proc Natl Acad Sci U S A. 43 : 416-421. PMID 16590032.
Hayes B. (1998). "The Invention of the Genetic Code." (PDF reprint). American Scientist 86 : 8-14.

Literature

Azimov A. Genetic code. From the theory of evolution to deciphering DNA. - M.: Tsentrpoligraf, 2006. - 208 pp. - ISBN 5-9524-2230-6.
Ratner V. A. Genetic code as a system - Soros educational journal, 2000, 6, No. 3, pp. 17-22.
Crick FH, Barnett L, Brenner S, Watts-Tobin RJ. General nature of the genetic code for proteins - Nature, 1961 (192), pp. 1227-32

Links

Genetic code- article from the Great Soviet Encyclopedia

Wikimedia Foundation. 2010.

Lecture 5. Genetic code

Definition of the concept

The genetic code is a system for recording information about the sequence of amino acids in proteins using the sequence of nucleotides in DNA.

Since DNA is not directly involved in protein synthesis, the code is written in RNA language. RNA contains uracil instead of thymine.

Properties of the genetic code

1. Triplety

Each amino acid is encoded by a sequence of 3 nucleotides.

Definition: a triplet or codon is a sequence of three nucleotides encoding one amino acid.

The code cannot be monoplet, since 4 (the number of different nucleotides in DNA) is less than 20. The code cannot be doublet, because 16 (the number of combinations and permutations of 4 nucleotides of 2) is less than 20. The code can be triplet, because 64 (the number of combinations and permutations from 4 to 3) is more than 20.

2. Degeneracy.

All amino acids, with the exception of methionine and tryptophan, are encoded by more than one triplet:

2 AK for 1 triplet = 2.

9 AK, 2 triplets each = 18.

1 AK 3 triplets = 3.

5 AK of 4 triplets = 20.

3 AK of 6 triplets = 18.

A total of 61 triplets encode 20 amino acids.

3. Presence of intergenic punctuation marks.

Definition:

Gene - a section of DNA that encodes one polypeptide chain or one molecule tRNA, rRNA orsRNA.

GenestRNA, rRNA, sRNAproteins are not coded.

At the end of each gene encoding a polypeptide there is at least one of 3 triplets encoding RNA stop codons, or stop signals. In mRNA they have the following form: UAA, UAG, UGA . They terminate (end) the broadcast.

Conventionally, the codon also belongs to punctuation marks AUG - the first after the leader sequence. (See Lecture 8) It functions as a capital letter. In this position it encodes formylmethionine (in prokaryotes).

4. Unambiguity.

Each triplet encodes only one amino acid or is a translation terminator.

The exception is the codon AUG . In prokaryotes, in the first position (capital letter) it encodes formylmethionine, and in any other position it encodes methionine.

5. Compactness, or absence of intragenic punctuation marks.
Within a gene, each nucleotide is part of a significant codon.

In 1961, Seymour Benzer and Francis Crick experimentally proved the triplet nature of the code and its compactness.

The essence of the experiment: “+” mutation - insertion of one nucleotide. "-" mutation - loss of one nucleotide. A single "+" or "-" mutation at the beginning of a gene spoils the entire gene. A double "+" or "-" mutation also spoils the entire gene.

A triple “+” or “-” mutation at the beginning of a gene spoils only part of it. A quadruple “+” or “-” mutation again spoils the entire gene.

The experiment proves that The code is transcribed and there is no punctuation marks inside the gene. The experiment was carried out on two adjacent phage genes and showed, in addition, presence of punctuation marks between genes.

6. Versatility.

The genetic code is the same for all creatures living on Earth.

In 1979, Burrell opened ideal human mitochondria code.

Definition:

“Ideal” is a genetic code in which the rule of degeneracy of the quasi-doublet code is satisfied: If in two triplets the first two nucleotides coincide, and the third nucleotides belong to the same class (both are purines or both are pyrimidines), then these triplets code for the same amino acid .

There are two exceptions to this rule in the universal code. Both deviations from the ideal code in the universal relate to fundamental points: the beginning and end of protein synthesis:

Codon	Universal code	Mitochondrial codes
Codon	Universal code	Vertebrates	Invertebrates	Yeast	Plants
	STOP				STOP

With UA
A G A		STOP
		STOP			230 substitutions do not change the class of the encoded amino acid. to tearability. In 1956, Georgiy Gamow proposed a variant of the overlapping code. According to the Gamow code, each nucleotide, starting from the third in the gene, is part of 3 codons. When the genetic code was deciphered, it turned out that it was non-overlapping, i.e. Each nucleotide is part of only one codon. Advantages of an overlapping genetic code: compactness, less dependence of the protein structure on the insertion or deletion of a nucleotide. Disadvantage: the protein structure is highly dependent on nucleotide replacement and restrictions on neighbors. In 1976, the DNA of phage φX174 was sequenced. It has single-stranded circular DNA consisting of 5375 nucleotides. The phage was known to encode 9 proteins. For 6 of them, genes located one after another were identified. It turned out that there is an overlap. Gene E is located entirely within the gene D . Its start codon results from a frame shift of one nucleotide. Gene J starts where the gene ends D . Start codon of the gene J overlaps with the stop codon of the gene D as a result of a shift of two nucleotides. The construction is called a “reading frame shift” by a number of nucleotides not a multiple of three. To date, overlap has only been shown for a few phages. Information capacity of DNA There are 6 billion people living on Earth. Hereditary information about them enclosed in 6x10 9 spermatozoa. According to various estimates, a person has from 30 to 50 thousand genes. All humans have ~30x10 13 genes, or 30x10 16 base pairs, which make up 10 17 codons. The average book page contains 25x10 2 characters. The DNA of 6x10 9 sperm contains information equal in volume to approximately 4x10 13 book pages. These pages would take up the space of 6 NSU buildings. 6x10 9 sperm take up half a thimble. Their DNA takes up less than a quarter of a thimble.

Genetic code– a unified system for recording hereditary information in nucleic acid molecules in the form of a nucleotide sequence. The genetic code is based on the use of an alphabet consisting of only four letters A, T, C, G, corresponding to DNA nucleotides. There are 20 types of amino acids in total. Of the 64 codons, three - UAA, UAG, UGA - do not code for amino acids; they were called nonsense codons and serve as punctuation marks. Codon (encoding trinucleotide) is a unit of genetic code, a trio of nucleotide residues (triplet) in DNA or RNA, encoding the inclusion of one amino acid. The genes themselves do not take part in protein synthesis. The mediator between gene and protein is mRNA. The structure of the genetic code is characterized by the fact that it is triplet, that is, it consists of triplets (triples) of nitrogenous DNA bases, called codons. Out of 64

Properties of the gene. code
1) Triplety: one amino acid is encoded by three nucleotides. These 3 nucleotides in DNA
are called triplet, in mRNA - codon, in tRNA - anticodon.
2) Redundancy (degeneracy): there are only 20 amino acids, and there are 61 triplets encoding amino acids, so each amino acid is encoded by several triplets.
3) Uniqueness: each triplet (codon) encodes only one amino acid.
4) Universality: the genetic code is the same for all living organisms on Earth.
5.) continuity and indisputability of codons during reading. This means that the nucleotide sequence is read triplet by triplet without gaps, and adjacent triplets do not overlap each other.

88. Heredity and variability are fundamental properties of living things. Darwin's understanding of the phenomena of heredity and variability.
Heredity call the general property of all organisms to preserve and transmit characteristics from parent to offspring. Heredity- this is the property of organisms to reproduce in generations a similar type of metabolism that has developed during the historical development of the species and manifests itself under certain environmental conditions.
Variability is the process of the emergence of qualitative differences between individuals of the same species, which is expressed either in a change under the influence of the external environment of only one phenotype, or in genetically determined hereditary variations resulting from combinations, recombinations and mutations that take place in a number of successive generations and populations.
Darwin's understanding of heredity and variability.
Under heredity Darwin understood the ability of organisms to preserve their species, varietal and individual characteristics in their offspring. This feature was well known and represented hereditary variation. Darwin analyzed in detail the importance of heredity in the evolutionary process. He drew attention to cases of same-suit hybrids of the first generation and splitting of characters in the second generation; he was aware of heredity associated with sex, hybrid atavisms and a number of other phenomena of heredity.
Variability. When comparing many breeds of animals and varieties of plants, Darwin noticed that within any species of animals and plants, and in culture, within any variety and breed there are no identical individuals. Darwin concluded that variability is inherent in all animals and plants.
Analyzing the material on the variability of animals, the scientist noticed that any change in living conditions is enough to cause variability. Thus, Darwin understood variability as the ability of organisms to acquire new characteristics under the influence of environmental conditions. He distinguished the following forms of variability:
Specific (group) variability(now called modification) - a similar change in all individuals of the offspring in one direction due to the influence of certain conditions. Certain changes tend to be non-hereditary.
Uncertain individual variability(now called genotypic) - the appearance of various minor differences in individuals of the same species, variety, breed, by which, existing in similar conditions, one individual differs from others. Such multidirectional variability is a consequence of the uncertain influence of living conditions on each individual.
Correlative(or relative) variability. Darwin understood the organism as an integral system, the individual parts of which are closely interconnected. Therefore, a change in the structure or function of one part often causes a change in another or others. An example of such variability is the relationship between the development of a functioning muscle and the formation of a ridge on the bone to which it is attached. Many wading birds have a correlation between neck length and limb length: birds with long necks also have long limbs.
Compensatory variability consists in the fact that the development of some organs or functions is often the cause of the inhibition of others, that is, there is an inverse correlation, for example, between milk production and meatiness of livestock.

89. Modification variability. Norm of reaction of genetically determined traits. Phenocopies.
Phenotypic variability covers changes in the state of the characteristics themselves that occur under the influence of developmental conditions or environmental factors. The range of modification variability is limited by the reaction norm. A specific modification change in a trait that has arisen is not inherited, but the range of modification variability is determined by heredity. Hereditary material is not involved in the change.
Norm of reaction is the limit of modification variability of a trait. It is the reaction norm that is inherited, not the modifications themselves, i.e. the ability to develop a trait, and the form of its manifestation depends on environmental conditions. The reaction norm is a specific quantitative and qualitative characteristic of the genotype. There are signs with a wide reaction norm, a narrow () and an unambiguous norm. Norm of reaction has limits or boundaries for each biological species (lower and upper) - for example, increased feeding will lead to an increase in the weight of the animal, but it will be within the normal reaction range characteristic of a given species or breed. The reaction rate is genetically determined and inherited. For different traits, the reaction norm limits vary greatly. For example, wide limits of the reaction norm are the value of milk yield, cereal productivity and many other quantitative characteristics, narrow limits are the color intensity of most animals and many other qualitative characteristics. Under the influence of some harmful factors that a person does not encounter in the process of evolution, the possibility of modification variability that determines reaction norms is excluded.
Phenocopies- changes in phenotype under the influence of unfavorable environmental factors, similar in manifestation to mutations. The resulting phenotypic modifications are not inherited. It has been established that the occurrence of phenocopies is associated with the influence of external conditions on a certain limited stage of development. Moreover, the same agent, depending on which phase it acts on, can copy different mutations, or one stage reacts to one agent, another to another. Different agents can be used to induce the same phenocopy, indicating that there is no connection between the result of the change and the influencing factor. The most complex genetic developmental disorders are relatively easy to reproduce, while copying traits is much more difficult.

90. Adaptive nature of modification. The role of heredity and environment in human development, training and education.
Modification variability corresponds to living conditions and is adaptive in nature. Characteristics such as the growth of plants and animals, their weight, color, etc. are subject to modification variability. The occurrence of modification changes is due to the fact that environmental conditions affect the enzymatic reactions occurring in the developing organism and, to a certain extent, change its course.
Since the phenotypic manifestation of hereditary information can be modified by environmental conditions, the organism’s genotype is programmed only with the possibility of their formation within certain limits, called the reaction norm. The reaction norm represents the limits of modification variability of a trait allowed for a given genotype.
The degree of expression of a trait when a genotype is realized under different conditions is called expressivity. It is associated with the variability of the trait within the reaction norm.
The same trait may appear in some organisms and be absent in others that have the same gene. A quantitative measure of the phenotypic expression of a gene is called penetrance.
Expressivity and penetrance are maintained by natural selection. Both patterns must be kept in mind when studying heredity in humans. By changing environmental conditions, penetrance and expressivity can be influenced. The fact that the same genotype can be the source of the development of different phenotypes is of significant importance for medicine. This means that the burden does not necessarily have to manifest itself. Much depends on the conditions in which a person finds himself. In some cases, diseases as a phenotypic manifestation of hereditary information can be prevented by following a diet or taking medications. The implementation of hereditary information depends on the environment. Formed on the basis of a historically established genotype, modifications are usually adaptive in nature, since they are always the result of responses of a developing organism to environmental factors affecting it. The nature of mutational changes is different: they are the result of changes in the structure of the DNA molecule, which causes a disruption in the previously established process of protein synthesis. When mice are kept at elevated temperatures, they produce offspring with elongated tails and enlarged ears. This modification is adaptive in nature, since the protruding parts (tail and ears) play a thermoregulatory role in the body: increasing their surface allows for increased heat transfer.

The genetic potential of a person is limited in time, and quite strictly. If you miss the deadline for early socialization, it will fade away before it has time to be realized. A striking example of this statement are the numerous cases when infants, by force of circumstances, ended up in the jungle and spent several years among animals. After their return to the human community, they could no longer fully catch up with what they had lost: master speech, acquire quite complex skills of human activity, their mental functions of a person developed poorly. This is evidence that the characteristic features of human behavior and activity are acquired only through social inheritance, only through the transmission of a social program in the process of upbringing and training.

Identical genotypes (in identical twins), when placed in different environments, can produce different phenotypes. Taking into account all the influencing factors, the human phenotype can be represented as consisting of several elements.

These include: biological inclinations encoded in genes; environment (social and natural); individual activity; mind (consciousness, thinking).

The interaction of heredity and environment in human development plays an important role throughout his life. But it acquires particular importance during the periods of formation of the body: embryonic, breast, childhood, adolescence and youth. It is at this time that an intensive process of development of the body and formation of personality is observed.

Heredity determines what an organism can become, but a person develops under the simultaneous influence of both factors - heredity and environment. Today it is becoming generally accepted that human adaptation is carried out under the influence of two programs of heredity: biological and social. All signs and properties of any individual are the result of the interaction of his genotype and environment. Therefore, each person is both a part of nature and a product of social development.

91. Combinative variability. The importance of combinative variability in ensuring the genotypic diversity of people: Marriage systems. Medical and genetic aspects of the family.
Combinative variability associated with obtaining new combinations of genes in the genotype. This is achieved as a result of three processes: a) independent chromosome segregation during meiosis; b) their random combination during fertilization; c) gene recombination due to Crossing Over. The hereditary factors (genes) themselves do not change, but their new combinations arise, which leads to the appearance of organisms with different genotypic and phenotypic properties. Thanks to combinative variability a variety of genotypes is created in the offspring, which is of great importance for the evolutionary process due to the fact that: 1) the diversity of material for the evolutionary process increases without reducing the viability of individuals; 2) the ability of organisms to adapt to changing environmental conditions expands and thereby ensures the survival of a group of organisms (population, species) as a whole

The composition and frequency of alleles in people and populations largely depend on the types of marriages. In this regard, the study of types of marriages and their medical and genetic consequences is important.

Marriages can be: selective, indiscriminate.

To the non-selective include panmix marriages. Panmixia(Greek nixis - mixture) - step marriages between people with different genotypes.

Selective marriages: 1.Outbreeding– marriages between people who are not related by a previously known genotype, 2.Inbreeding- marriages between relatives, 3.Positively assortative– marriages between individuals with similar phenotypes (deaf-mute, short with short, tall with tall, feeble-minded with feeble-minded, etc.). 4.Negative assortative-marriages between people with dissimilar phenotypes (deaf-mute - normal; short - tall; normal - with freckles, etc.). 4.Incest– marriages between close relatives (between brother and sister).

Inbred and incestuous marriages are illegal in many countries. Unfortunately, there are regions with a high frequency of inbred marriages. Until recently, the frequency of inbred marriages in some regions of Central Asia reached 13-15%.

Medical and genetic significance inbred marriages are very negative. In such marriages, homozygotization is observed, and the frequency of autosomal recessive diseases increases by 1.5-2 times. Inbred populations experience inbreeding depression, i.e. the frequency of unfavorable recessive alleles increases sharply, and child mortality increases. Positively assortative marriages also lead to similar phenomena. Outbreeding has positive genetic benefits. In such marriages, heterozygotization is observed.

92. Mutational variability, classification of mutations according to the level of change in the damage to the hereditary material. Mutations in germ and somatic cells.
Mutation is called a change caused by the reorganization of reproductive structures, a change in its genetic apparatus. Mutations occur spasmodically and are inherited. Depending on the level of change in the hereditary material, all mutations are divided into genetic, chromosomal And genomic.
Gene mutations, or transgenations, affect the structure of the gene itself. Mutations can change sections of the DNA molecule of varying lengths. The smallest region, the change of which leads to the appearance of a mutation, is called a muton. It can only be made up of a pair of nucleotides. A change in the sequence of nucleotides in DNA causes a change in the sequence of triplets and, ultimately, the protein synthesis program. It should be remembered that disturbances in the DNA structure lead to mutations only when repair is not carried out.
Chromosomal mutations, chromosomal rearrangements or aberrations consist of a change in the amount or redistribution of the hereditary material of chromosomes.
Perestroikas are divided into intrachromosomal And interchromosomal. Intrachromosomal rearrangements consist of the loss of part of a chromosome (deletion), doubling or multiplication of some of its sections (duplication), and rotation of a chromosome fragment by 180° with a change in the sequence of gene location (inversion).
Genomic mutations associated with changes in the number of chromosomes. Genomic mutations include aneuploidy, haploidy and polyploidy.
Aneuploidy called a change in the number of individual chromosomes - the absence (monosomy) or the presence of additional (trisomy, tetrasomy, generally polysomy) chromosomes, i.e. an unbalanced chromosome set. Cells with an altered number of chromosomes appear as a result of disturbances in the process of mitosis or meiosis, and therefore a distinction is made between mitotic and meiotic aneuploidy. A multiple decrease in the number of chromosome sets of somatic cells compared to diploid is called haploidy. A multiple increase in the number of chromosome sets of somatic cells compared to diploid is called polyploidy.
The listed types of mutations occur in both germ cells and somatic cells. Mutations that occur in germ cells are called generative. They are passed on to subsequent generations.
Mutations that occur in bodily cells at one or another stage of the individual development of the organism are called somatic. Such mutations are inherited only by the descendants of the cell in which it occurred.

93. Gene mutations, molecular mechanisms of occurrence, frequency of mutations in nature. Biological antimutation mechanisms.
Modern genetics emphasizes that gene mutations consist in changing the chemical structure of genes. Specifically, gene mutations are substitutions, insertions, deletions, and losses of nucleotide pairs. The smallest section of a DNA molecule whose change leads to mutation is called a muton. It is equal to one pair of nucleotides.
There are several classifications of gene mutations . Spontaneous(spontaneous) is a mutation that occurs without direct connection with any physical or chemical environmental factor.
If mutations are caused intentionally, by influencing the body by factors of a known nature, they are called induced. The agent that induces mutations is called mutagen.
The nature of mutagens is diverse- these are physical factors, chemical compounds. The mutagenic effect of some biological objects - viruses, protozoa, helminths - when they penetrate the human body has been established.
As a result of dominant and recessive mutations, dominant and recessive altered traits appear in the phenotype. Dominant mutations appear in the phenotype already in the first generation. Recessive mutations are hidden in heterozygotes from the action of natural selection, so they accumulate in large numbers in the gene pools of species.
An indicator of the intensity of the mutation process is the mutation frequency, which is calculated on average per genome or separately for specific loci. The average mutation frequency is comparable in a wide range of living beings (from bacteria to humans) and does not depend on the level and type of morphophysiological organization. It is equal to 10 -4 - 10 -6 mutations per 1 locus per generation.
Antimutation mechanisms.
A protective factor against the adverse consequences of gene mutations is the pairing of chromosomes in the diploid karyotype of somatic eukaryotic cells. The pairing of alley genes prevents the phenotypic manifestation of mutations if they are recessive.
The phenomenon of extracopying genes encoding vital macromolecules contributes to reducing the harmful consequences of gene mutations. For example, the genes of rRNA, tRNA, histone proteins, without which the life of any cell is impossible.
The listed mechanisms contribute to the preservation of genes selected during evolution and at the same time the accumulation of different alleles in the gene pool of a population, forming a reserve of hereditary variability.

94. Genomic mutations: polyploidy, haploidy, heteroploidy. Mechanisms of their occurrence.
Genomic mutations are associated with changes in the number of chromosomes. Genomic mutations include heteroploidy, haploidy And polyploidy.
Polyploidy– an increase in the diploid number of chromosomes by adding entire chromosome sets as a result of disruption of meiosis.
In polyploid forms, there is an increase in the number of chromosomes, a multiple of the haploid set: 3n – triploid; 4n – tetraploid, 5n – pentaploid, etc.
Polyploid forms are phenotypically different from diploid ones: along with a change in the number of chromosomes, hereditary properties also change. In polyploids, the cells are usually large; sometimes the plants are gigantic in size.
Forms resulting from the multiplication of chromosomes of one genome are called autoploid. However, another form of polyploidy is also known - alloploidy, in which the number of chromosomes of two different genomes is multiplied.
A multiple decrease in the number of chromosome sets of somatic cells compared to diploid is called haploidy. Haploid organisms in natural habitats are found mainly among plants, including higher ones (datura, wheat, corn). The cells of such organisms have one chromosome of each homologous pair, so all recessive alleles are manifested in the phenotype. This explains the reduced viability of haploids.
Heteroploidy. As a result of disturbances in mitosis and meiosis, the number of chromosomes may change and not become a multiple of the haploid set. The phenomenon when one of the chromosomes, instead of being a pair, ends up in a triple number, is called trisomy. If trisomy is observed on one chromosome, then such an organism is called trisomic and its chromosome set is 2n+1. Trisomy can be on any of the chromosomes or even on several. With Double trisomy, it has a chromosome set of 2n+2, triple trisomy – 2n+3, etc.
The opposite phenomenon trisomy, i.e. the loss of one chromosome from a pair in a diploid set is called monosomy, the organism is monosomic; its genotypic formula is 2n-1. In the absence of two different chromosomes, the organism is double monosomic with the genotypic formula 2n-2, etc.
From what has been said it is clear that aneuploidy, i.e. a violation of the normal number of chromosomes leads to changes in the structure and a decrease in the viability of the organism. The greater the disturbance, the lower the viability. In humans, disruption of a balanced set of chromosomes leads to painful conditions known collectively as chromosomal diseases.
Mechanism of occurrence genomic mutations are associated with the pathology of disruption of normal chromosome segregation in meiosis, resulting in the formation of abnormal gametes, which leads to mutation. Changes in the body are associated with the presence of genetically heterogeneous cells.

95. Methods for studying human heredity. Genealogical and twin methods, their significance for medicine.
The main methods for studying human heredity are genealogical, twin, population-statistical, dermatoglyphics method, cytogenetic, biochemical, somatic cell genetics method, modeling method
Genealogical method. This method is based on the compilation and analysis of pedigrees. A pedigree is a diagram that shows the connections between family members. By analyzing pedigrees, they study any normal or (more often) pathological trait in generations of people who are related.
Genealogical methods are used to determine the hereditary or non-hereditary nature of a trait, dominance or recessivity, chromosome mapping, sex linkage, and to study the mutation process. As a rule, the genealogical method forms the basis for conclusions in medical genetic counseling.
When compiling pedigrees, standard notations are used. The person with whom the study begins is the proband. The descendant of a married couple is called a sibling, siblings are called siblings, cousins are called first cousins, etc. Descendants who have a common mother (but different fathers) are called consanguineous, and descendants who have a common father (but different mothers) are called half-blooded; if a family has children from different marriages, and they do not have common ancestors (for example, a child from the mother’s first marriage and a child from the father’s first marriage), then they are called step-children.
Using the genealogical method, the hereditary nature of the trait being studied can be established, as well as the type of its inheritance. When analyzing pedigrees for several characteristics, the linked nature of their inheritance can be revealed, which is used in the compilation of chromosomal maps. This method allows you to study the intensity of the mutation process, assess the expressivity and penetrance of the allele.
Twin method. It consists of studying the patterns of inheritance of traits in pairs of identical and fraternal twins. Twins are two or more children conceived and born by the same mother almost simultaneously. There are identical and fraternal twins.
Identical (monozygotic, identical) twins occur at the earliest stages of zygote fragmentation, when two or four blastomeres retain the ability to develop into a full-fledged organism when separated. Because the zygote divides by mitosis, the genotypes of identical twins are, at least initially, completely identical. Identical twins are always the same sex and share the same placenta during fetal development.
Fraternal (dizygotic, non-identical) occur when two or more simultaneously matured eggs are fertilized. Thus, they share about 50% of their genes. In other words, they are similar to ordinary brothers and sisters in their genetic constitution and can be either same-sex or opposite-sex.
By comparing identical and fraternal twins raised in the same environment, conclusions can be drawn about the role of genes in the development of traits.
The twin method allows you to make informed conclusions about the heritability of traits: the role of heredity, environment and random factors in determining certain human traits
Prevention and diagnosis of hereditary pathology
Currently, the prevention of hereditary pathology is carried out at four levels: 1) pregametic; 2) prezygotic; 3) prenatal; 4) neonatal.
1.) Pregametic level
Carried out:
1. Sanitary control over production - eliminating the influence of mutagens on the body.
2. Liberation of women of childbearing age from work in hazardous industries.
3.Creation of lists of hereditary diseases that are common in a certain area
territories with def. frequent.
2.Prezygotic level
The most important element of this level of prevention is medical genetic counseling (MGC) of the population, informing the family about the degree of possible risk of having a child with a hereditary pathology and providing assistance in making the right decision about childbearing.
Prenatal level
It consists of carrying out prenatal (prenatal) diagnostics.
Prenatal diagnosis– this is a set of measures that is carried out with the aim of determining hereditary pathology in the fetus and terminating this pregnancy. Prenatal diagnostic methods include:
1. Ultrasound scanning (USS).
2. Fetoscopy– a method of visual observation of the fetus in the uterine cavity through an elastic probe equipped with an optical system.
3. Chorionic villus biopsy. The method is based on taking chorionic villi, culturing cells and studying them using cytogenetic, biochemical and molecular genetic methods.
4. Amniocentesis– puncture of the amniotic sac through the abdominal wall and collection
amniotic fluid. It contains fetal cells that can be examined
cytogenetically or biochemically, depending on the expected pathology of the fetus.
5. Cordocentesis- puncture of the umbilical cord vessels and collection of fetal blood. Fetal lymphocytes
cultivated and subjected to research.
4.Neonatal level
At the fourth level, newborns are screened to identify autosomal recessive metabolic diseases in the preclinical stage, when timely treatment begins to ensure normal mental and physical development of children.

Principles of treatment of hereditary diseases
The following types of treatment are available:.
1. Symptomatic(impact on disease symptoms).
2. Pathogenetic(impact on the mechanisms of disease development).
Symptomatic and pathogenetic treatment does not eliminate the causes of the disease, because does not liquidate
genetic defect.
The following techniques can be used in symptomatic and pathogenetic treatment.
· Correction developmental defects using surgical methods (syndactyly, polydactyly,
cleft lip...
· Replacement therapy, the meaning of which is to introduce into the body
missing or insufficient biochemical substrates.
· Metabolism induction– introduction into the body of substances that enhance synthesis
some enzymes and, therefore, speed up processes.
· Metabolism inhibition– introduction into the body of drugs that bind and remove
abnormal metabolic products.
· Diet therapy ( therapeutic nutrition) - elimination from the diet of substances that
cannot be absorbed by the body.
Prospects: In the near future, genetics will develop rapidly, although it is still
very widespread in agricultural crops (breeding, cloning),
medicine (medical genetics, genetics of microorganisms). In the future, scientists hope
use genetics to eliminate defective genes and eradicate diseases transmitted
by inheritance, to be able to treat such serious diseases as cancer, viral
infections.

With all the shortcomings of the modern assessment of the radiogenetic effect, there is no doubt about the seriousness of the genetic consequences awaiting humanity in the event of an uncontrolled increase in the radioactive background in the environment. The danger of further testing of atomic and hydrogen weapons is obvious.
At the same time, the use of atomic energy in genetics and selection makes it possible to create new methods for controlling the heredity of plants, animals and microorganisms, and to better understand the processes of genetic adaptation of organisms. In connection with human flights into outer space, there is a need to study the influence of the cosmic reaction on living organisms.

98. Cytogenetic method for diagnosing human chromosomal disorders. Amniocentesis. Karyotype and idiogram of human chromosomes. Biochemical method.
The cytogenetic method involves studying chromosomes using a microscope. Most often, the object of study is mitotic (metaphase), less often meiotic (prophase and metaphase) chromosomes. Cytogenetic methods are used to study the karyotypes of individual individuals
Obtaining material from an organism developing in utero is carried out in different ways. One of them is amniocentesis, with the help of which, at 15-16 weeks of pregnancy, amniotic fluid is obtained, containing waste products of the fetus and cells of its skin and mucous membranes
The material taken during amniocentesis is used for biochemical, cytogenetic and molecular chemical studies. Cytogenetic methods determine the sex of the fetus and identify chromosomal and genomic mutations. The study of amniotic fluid and fetal cells using biochemical methods makes it possible to detect a defect in the protein products of genes, but does not make it possible to determine the localization of mutations in the structural or regulatory part of the genome. The use of DNA probes plays an important role in identifying hereditary diseases and precise localization of damage to the fetal hereditary material.
Currently, amniocentesis is used to diagnose all chromosomal abnormalities, over 60 hereditary metabolic diseases, and incompatibility of mother and fetus with erythrocyte antigens.
The diploid set of chromosomes of a cell, characterized by their number, size and shape, is called karyotype. A normal human karyotype includes 46 chromosomes, or 23 pairs: 22 pairs of autosomes and one pair of sex chromosomes
In order to make it easier to understand the complex complex of chromosomes that makes up the karyotype, they are arranged in the form idiograms. IN idiogram chromosomes are arranged in pairs in order of decreasing size, with the exception of sex chromosomes. The largest pair is assigned No. 1, the smallest - No. 22. Identification of chromosomes only by size encounters great difficulties: a number of chromosomes have similar sizes. However, in Lately By using various types of dyes, a clear differentiation of human chromosomes along their length into bands that can be dyed using special methods and those that cannot be dyed has been established. The ability to accurately differentiate chromosomes is of great importance for medical genetics, as it allows one to accurately determine the nature of abnormalities in a person’s karyotype.
Biochemical method

99. Human karyotype and idiogram. Characteristics of a normal human karyotype
and pathology.
Karyotype- a set of characteristics (number, size, shape, etc.) of the complete set of chromosomes,
inherent in the cells of a given biological species (species karyotype), of a given organism
(individual karyotype) or line (clone) of cells.
To determine the karyotype, a microphotograph or sketch of chromosomes is used during microscopy of dividing cells.
Each person has 46 chromosomes, two of which are sex chromosomes. A woman has two X chromosomes
(karyotype: 46, XX), and men have one X chromosome and the other Y (karyotype: 46, XY). Study
Karyotyping is carried out using a method called cytogenetics.
Idiogram- a schematic representation of the haploid set of chromosomes of an organism, which
placed in a row in accordance with their sizes, in pairs in descending order of their sizes. An exception is made for sex chromosomes, which are especially distinguished.
Examples of the most common chromosomal pathologies.
Down syndrome is a trisomy of the 21st pair of chromosomes.
Edwards syndrome is trisomy on the 18th pair of chromosomes.
Patau syndrome is a trisomy of the 13th pair of chromosomes.
Klinefelter syndrome is a polysomy of the X chromosome in boys.

100. The importance of genetics for medicine. Cytogenetic, biochemical, population-statistical methods for studying human heredity.
The role of genetics in human life is very important. It is implemented with the help of medical genetic counseling. Medical genetic counseling is designed to save humanity from suffering associated with hereditary (genetic) diseases. The main goals of medical genetic counseling are to establish the role of the genotype in the development of this disease and predict the risk of having sick offspring. Recommendations given in medical genetic consultations regarding marriage or prognosis of the genetic usefulness of offspring are aimed at ensuring that they are taken into account by the persons being consulted, who voluntarily make the appropriate decision.
Cytogenetic (karyotypic) method. The cytogenetic method involves studying chromosomes using a microscope. Most often, the object of study is mitotic (metaphase), less often meiotic (prophase and metaphase) chromosomes. This method is also used to study sex chromatin ( Barr bodies) Cytogenetic methods are used to study the karyotypes of individual individuals
The use of the cytogenetic method allows not only to study the normal morphology of chromosomes and the karyotype as a whole, to determine the genetic sex of the organism, but, most importantly, to diagnose various chromosomal diseases associated with changes in the number of chromosomes or disruption of their structure. In addition, this method allows you to study mutagenesis processes at the chromosome and karyotype levels. Its use in medical genetic counseling for the purposes of prenatal diagnosis of chromosomal diseases makes it possible, through timely termination of pregnancy, to prevent the appearance of offspring with severe developmental disorders.
Biochemical method consists of determining the activity of enzymes or the content of certain metabolic products in the blood or urine. Using this method, metabolic disorders caused by the presence in the genotype of an unfavorable combination of allelic genes, most often recessive alleles in a homozygous state, are identified. With timely diagnosis of such hereditary diseases, preventive measures make it possible to avoid serious developmental disorders.
Population statistical method. This method allows you to estimate the probability of birth of individuals with a certain phenotype in a given population group or in consanguineous marriages; calculate the frequency of carriage in the heterozygous state of recessive alleles. The method is based on the Hardy-Weinberg law. Hardy-Weinberg Law- This is the law of population genetics. The law states: “In an ideal population, the frequencies of genes and genotypes remain constant from generation to generation.”
The main features of human populations are: common territory and the possibility of free marriage. Factors of isolation, i.e. restriction of a person’s freedom of choice of spouses, can be not only geographical, but also religious and social barriers.
In addition, this method makes it possible to study the mutation process, the role of heredity and environment in the formation of human phenotypic polymorphism according to normal characteristics, as well as in the occurrence of diseases, especially with a hereditary predisposition. The population statistical method is used to determine the significance of genetic factors in anthropogenesis, in particular in race formation.

101.Structural disorders (aberrations) of chromosomes. Classification depending on changes in genetic material. Implications for biology and medicine.
Chromosomal aberrations result from chromosome rearrangements. They are a consequence of a chromosome break, leading to the formation of fragments that are subsequently reunited, but the normal structure of the chromosome is not restored. There are 4 main types of chromosomal aberrations: shortage, doublings, inversions, translocations, deletion- loss of a specific chromosome region, which is then usually destroyed
Shortages arise due to the loss of a chromosome of one or another region. Deficiencies in the middle part of the chromosome are called deletions. The loss of a significant part of a chromosome leads to death of the organism, the loss of minor sections causes a change in hereditary properties. So. When corn is missing one of its chromosomes, its seedlings lack chlorophyll.
Doubling associated with the inclusion of an extra, duplicating section of the chromosome. This also leads to the appearance of new symptoms. Thus, in Drosophila, the gene for stripe-shaped eyes is caused by the doubling of a section of one of the chromosomes.
Inversions observed when a chromosome breaks and the torn section is turned 180 degrees. If the break occurs in one place, the detached fragment is attached to the chromosome with the opposite end, but if in two places, then the middle fragment, turning over, is attached to the places of the break, but with different ends. According to Darwin, inversions play an important role in the evolution of species.
Translocations arise in cases when a section of a chromosome from one pair is attached to a non-homologous chromosome, i.e. chromosome from another pair. Translocation sections of one of the chromosomes are known in humans; it may be the cause of Down's syndrome. Most translocations affecting large sections of chromosomes render the organism nonviable.
Chromosomal mutations change the dose of some genes, cause redistribution of genes between linkage groups, change their localization in the linkage group. By doing this, they disrupt the gene balance of the body's cells, resulting in deviations in the somatic development of the individual. As a rule, changes extend to several organ systems.
Chromosomal aberrations are of great importance in medicine. At chromosomal aberrations, there is a delay in general physical and mental development. Chromosomal diseases are characterized by a combination of many congenital defects. This defect is a manifestation of Down syndrome, which is observed in the case of trisomy on a small segment of the long arm of chromosome 21. The picture of cat cry syndrome develops with the loss of a section of the short arm of chromosome 5. In humans, malformations of the brain, musculoskeletal, cardiovascular, and genitourinary systems are most often observed.

102. The concept of species, modern views on speciation. Type criteria.
View is a collection of individuals that are similar in terms of species criteria to such an extent that they can
naturally interbreed and produce fertile offspring.
Fertile offspring- something that can reproduce itself. An example of infertile offspring is a mule (a hybrid of a donkey and a horse), it is infertile.
Type criteria- these are characteristics by which 2 organisms are compared to determine whether they belong to the same species or to different ones.
· Morphological – internal and external structure.
· Physiological-biochemical – how organs and cells work.
· Behavioral – behavior, especially at the time of reproduction.
· Ecological – a set of environmental factors necessary for life
type (temperature, humidity, food, competitors, etc.)
· Geographical – area (area of distribution), i.e. the territory in which the species lives.
· Genetic-reproductive – the same number and structure of chromosomes, which allows organisms to produce fertile offspring.
Type criteria are relative, i.e. A species cannot be judged by one criterion. For example, there are twin species (in the malaria mosquito, in rats, etc.). They do not differ morphologically from each other, but have different quantities chromosomes and therefore do not produce offspring.

103.Population. Its ecological and genetic characteristics and role in speciation.
Population- a minimal self-reproducing group of individuals of the same species, more or less isolated from other similar groups, inhabiting a certain area for a long series of generations, forming its own genetic system and forming its own ecological niche.
Ecological indicators of the population.
Number- the total number of individuals in the population. This value is characterized by a wide range of variability, but it cannot be below certain limits.
Density- the number of individuals per unit area or volume. As numbers increase, population density tends to increase
Spatial structure A population is characterized by the peculiarities of the distribution of individuals in the occupied territory. It is determined by the properties of the habitat and the biological characteristics of the species.
Sexual structure reflects a certain ratio of male and female individuals in the population.
Age structure reflects the ratio of different age groups in populations, depending on life expectancy, time of puberty, and the number of descendants.
Genetic indicators of the population. Genetically, a population is characterized by its gene pool. It is represented by a set of alleles that form the genotypes of organisms in a given population.
When describing populations or comparing them with each other, a number of genetic characteristics are used. Polymorphism. A population is called polymorphic at a given locus if two or more alleles occur in it. If a locus is represented by a single allele, we speak of monomorphism. By examining many loci, it is possible to determine the proportion of polymorphic ones among them, i.e. assess the degree of polymorphism, which is an indicator of the genetic diversity of the population.
Heterozygosity. An important genetic characteristic of a population is heterozygosity - the frequency of heterozygous individuals in the population. It also reflects genetic diversity.
Coefficient of inbreeding. This coefficient is used to estimate the prevalence of inbreeding in a population.
Gene association. Allele frequencies of different genes can depend on each other, which is characterized by association coefficients.
Genetic distances. Different populations differ from each other in allele frequencies. To quantify these differences, metrics called genetic distances have been proposed.

Population– elementary evolutionary structure. In the range of any species, individuals are distributed unevenly. Areas of dense concentration of individuals alternate with spaces where there are few or none of them. As a result, more or less isolated populations arise in which random free interbreeding (panmixia) systematically occurs. Interbreeding with other populations occurs very rarely and irregularly. Thanks to panmixia, a characteristic gene pool is created in each population, different from other populations. It is the population that should be recognized as the elementary unit of the evolutionary process

The role of populations is great, since almost all mutations occur within it. These mutations are primarily associated with isolated populations and gene pools that differ due to their isolation from each other. The material for evolution is mutational variability, which begins in a population and ends with the formation of a species.

GENETIC CODE, a method of recording hereditary information in nucleic acid molecules in the form of a sequence of nucleotides forming these acids. A certain sequence of nucleotides in DNA and RNA corresponds to a certain sequence of amino acids in the polypeptide chains of proteins. It is customary to write the code using capital letters of Russian or Latin alphabet. Each nucleotide is designated by the letter with which the name of the nitrogenous base included in its molecule begins: A (A) - adenine, G (G) - guanine, C (C) - cytosine, T (T) - thymine; in RNA, instead of thymine, uracil is U (U). Each is encoded by a combination of three nucleotides – a triplet, or codon. Briefly, the path of transfer of genetic information is summarized in the so-called. The central dogma of molecular biology: DNA ` RNA f protein.

In special cases, information can be transferred from RNA to DNA, but never from proteins to genes.

The implementation of genetic information is carried out in two stages. In the cell nucleus, informational, or matrix, RNA (transcription) is synthesized on DNA. In this case, the DNA nucleotide sequence is “rewritten” (recoded) into the mRNA nucleotide sequence. Then the mRNA passes into the cytoplasm, attaches to the ribosome, and on it, as on a matrix, the polypeptide chain of the protein is synthesized (translation). Amino acids are attached to the chain under construction using transfer RNA in a sequence determined by the order of nucleotides in the mRNA.

From four “letters” you can make 64 different three-letter “words” (codons). Of the 64 codons, 61 encode specific amino acids, and three are responsible for completing the synthesis of the polypeptide chain. Since there are 61 codons per 20 amino acids that make up proteins, some amino acids are coded by more than one codon (so-called code degeneracy). This redundancy increases the reliability of the code and the entire mechanism of protein biosynthesis. Another property of the code is its specificity (unambiguity): one codon encodes only one amino acid.

In addition, the code does not overlap - information is read in one direction sequentially, triplet by triplet. The most amazing property of the code is its universality: it is the same in all living beings - from bacteria to humans (with the exception of the genetic code of mitochondria). Scientists see this as confirmation of the concept that all organisms descend from one common ancestor.

Deciphering the genetic code, i.e. determining the “meaning” of each codon and the rules by which information is read, was carried out in 1961–1965. and is considered one of the most striking achievements of molecular biology.

The series of articles describing the origins of the Civil Code can be treated as an investigation into events about which we have a lot of traces left. However, understanding these articles requires some effort to understand the molecular mechanisms of protein synthesis. This article is the introductory one for a series of auto-publications devoted to the origin of the genetic code, and is the best place to start getting acquainted with this topic.
Usually genetic code(GC) is defined as a method (rule) for encoding a protein on the primary structure of DNA or RNA. In the literature, it is most often written that this is a unique correspondence of a sequence of three nucleotides in a gene to one amino acid in a synthesized protein or the end point of protein synthesis. However, there are two errors in this definition. This refers to 20 so-called canonical amino acids, which are part of the proteins of all living organisms without exception. These amino acids are protein monomers. The errors are as follows:

1) There are not 20 canonical amino acids, but only 19. We can call an amino acid a substance that simultaneously contains an amino group -NH 2 and a carboxyl group - COOH. The fact is that the protein monomer - proline - is not an amino acid, since it contains an imino group instead of an amino group, therefore it is more correct to call proline an imino acid. However, in the future, in all articles devoted to HA, for convenience, I will write about 20 amino acids, implying the specified nuance. Amino acid structures are shown in Fig. 1.

Rice. 1. Structures of canonical amino acids. Amino acids have constant parts, indicated in black in the figure, and variable parts (or radicals), indicated in red.

2) The correspondence of amino acids to codons is not always unambiguous. For violation of cases of unambiguity, see below.

The emergence of GC means the emergence of encoded protein synthesis. This event is one of the key events for the evolutionary formation of the first living organisms.

The structure of HA is presented in a circular form in Fig. 2.

Rice. 2. Genetic code in a circular shape. The inner circle is the first letter of the codon, the second circle - the second letter of the codon, the third circle - the third letter of the codon, the fourth circle - the designation of amino acids in a three-letter abbreviation; P - polar amino acids, NP - non-polar amino acids. For clarity of symmetry, the chosen order of symbols is important U - C - A - G .

So, let's begin to describe the main properties of HA.

1. Tripletity. Each amino acid is encoded by a sequence of three nucleotides.

2. Presence of intergenic punctuation marks. Intergenic punctuation marks include nucleic acid sequences at which translation begins or ends.

Translation can not begin from any codon, but only from a strictly defined one - starting. The start codon includes the AUG triplet, from which translation begins. In this case, this triplet encodes either methionine or another amino acid - formylmethionine (in prokaryotes), which can only be included at the beginning of protein synthesis. At the end of each gene encoding a polypeptide there is at least one of 3 stop codons, or brake lights: UAA, UAG, UGA. They terminate translation (the so-called protein synthesis on the ribosome).

3. Compactness, or absence of intragenic punctuation marks. Within a gene, each nucleotide is part of a significant codon.

4. Non-overlapping. Codons do not overlap with each other; each has its own ordered set of nucleotides, which does not overlap with similar sets of neighboring codons.

5. Degeneracy. The reverse correspondence in the amino acid-to-codon direction is ambiguous. This property is called degeneracy. Series is a set of codons that code for one amino acid, in other words, it is a group equivalent codons. Let's think of a codon as XYZ. If XY specifies the “sense” (i.e., an amino acid), then the codon is called strong. If, to determine the meaning of a codon, a certain Z is needed, then such a codon is called weak.

The degeneracy of the code is closely related to the ambiguity of codon-anticodon pairing (an anticodon means a sequence of three nucleotides on tRNA, which can complementarily pair with a codon on messenger RNA (see two articles for more details on this: Molecular mechanisms for ensuring code degeneracy And Lagerquist's rule. Physico-chemical justification of Rumer's symmetries and relations). One anticodon on a tRNA can recognize one to three codons on an mRNA.

6.Unambiguity. Each triplet encodes only one amino acid or is a translation terminator.

There are three known exceptions.

First. In prokaryotes, in the first position (capital letter), it encodes formylmethionine, and in any other position, methionine. At the beginning of the gene, formylmethionine is encoded by both the usual methionine codon AUG and also the valine codon GUG or leucine UUG, which within the gene encode valine and leucine, respectively .

In many proteins, formylmethionine is cleaved or the formyl group is removed, resulting in formylmethionine being converted to regular methionine.

Second. In 1986, several groups of researchers discovered that the UGA stop codon on mRNA can encode selenocysteine (see Fig. 3), provided that it is followed by a special nucleotide sequence.

Rice. 3. Structure of the 21st amino acid - selenocysteine.

U E. coli(this is the Latin name for Escherichia coli) selenocysteyl-tRNA during translation recognizes the UGA codon in mRNA, but only in a certain context: for the UGA codon to be recognized as meaningful, a sequence of 45 nucleotides in length located after the UGA codon is important.

The considered example shows that, if necessary, a living organism can change the meaning of the standard genetic code. In this case, the genetic information contained in the genes is encoded in a more complex way. The meaning of a codon is determined in the context of a specific extended nucleotide sequence and with the participation of several highly specific protein factors. It is important that selenocysteine tRNA was found in representatives of all three branches of life (archaea, eubacteria and eukaryotes), which indicates the ancient origin of selenocysteine synthesis, and its possible presence in the last universal common ancestor (which will be discussed in other articles). Most likely, selenocysteine is found in all living organisms without exception. But in any given organism, selenocysteine is found in no more than dozens of proteins. It is part of the active centers of enzymes, in a number of homologues of which ordinary cysteine can function in a similar position.

Until recently, it was believed that the UGA codon could be read as either selenocysteine or terminal, but it has recently been shown that in ciliates Euplotes The UGA codon encodes either cysteine or selenocysteine. Cm. " Genetic code allows for discrepancies"

Third exception. Some prokaryotes (5 species of archaea and one eubacterium - the information on Wikipedia is very outdated) contain a special acid - pyrrolysine (Fig. 4). It is encoded by the UAG triplet, which in the canonical code serves as a translation terminator. It is assumed that in this case, similar to the case with selenocysteine encoding, the reading of UAG as a pyrrolysine codon occurs due to a special structure on the mRNA. Pyrrolysine tRNA contains the anticodon CTA and is aminoacylated by class 2 ARSases (for the classification of ARSases, see the article “Codases help to understand how the genetic code ").

UAG is rarely used as a stop codon, and when it is used, it is often followed by another stop codon.

Rice. 4. Structure of the 22nd amino acid of pyrrolysine.

7. Versatility. After the deciphering of the Civil Code was completed in the mid-60s of the last century, it was believed for a long time that the code was the same in all organisms, which indicates the unity of origin of all life on Earth.

Let's try to understand why the Civil Code is universal. The fact is that if at least one coding rule were to change in the body, this would lead to a change in the structure of a significant part of the proteins. Such a change would be too drastic and therefore almost always lethal, since a change in the meaning of just one codon can affect on average 1/64 of all amino acid sequences.

This leads to one very important idea: the GC has hardly changed since its formation more than 3.5 billion years ago. This means that its structure bears a trace of its origin, and analysis of this structure can help to understand exactly how the GC could have arisen.

In fact, HA may differ somewhat in bacteria, mitochondria, the nuclear code of some ciliates and yeast. Currently, there are at least 17 genetic codes that differ from the canonical one by 1-5 codons. In total, in all known variants of deviations from the universal GK, 18 different substitutions of the meaning of a codon are used. The most deviations from the standard code are known for mitochondria - 10. It is noteworthy that the mitochondria of vertebrates, flatworms, and echinoderms are encoded by different codes, and mold fungi, protozoa and coelenterates are encoded by one.

The evolutionary proximity of species does not at all guarantee that they have similar GCs. Genetic codes can vary even between different mycoplasma species (some species have a canonical code, while others have divergent ones). A similar situation is observed for yeast.

It is important to note that mitochondria are descendants of symbiotic organisms that have adapted to live inside cells. They have a greatly reduced genome; some genes have moved to the cell nucleus. Therefore, changes in the HA in them are no longer so dramatic.

Exceptions discovered later are of particular interest from an evolutionary point of view, since they can help shed light on the mechanisms of code evolution.

Table 1.

Mitochondrial codes in various organisms.

Codon	Universal code	Mitochondrial codes
Codon	Universal code	Vertebrates	Invertebrates	Yeast	Plants
U.G.A.	STOP	Trp	Trp	Trp	STOP
AUA	Ile	Met	Met	Met	Ile
CUA	Leu	Leu	Leu	Thr	Leu
A.G.A.	Arg	STOP	Ser	Arg	Arg
AGG	Arg	STOP	Ser	Arg	Arg

Three mechanisms for changing the amino acid encoded by the code.

The first is when a certain codon is not used (or almost not used) by some organism due to the uneven occurrence of some nucleotides (GC composition), or combinations of nucleotides. As a result, such a codon may completely disappear from use (for example, due to the loss of the corresponding tRNA), and can later be used to encode another amino acid without causing significant damage to the body. This mechanism may be responsible for the emergence of some code dialects in mitochondria.

The second is the transformation of the stop codon into the sense of ova. In this case, some of the translated proteins may have additions. However, the situation is partially saved by the fact that many genes often end with not one, but two stop codons, since translation errors are possible, in which stop codons are read as amino acids.

The third is possible ambiguous reading of certain codons, as is the case in some fungi.

8 . Connectivity. Groups of equivalent codons (that is, codons that code for the same amino acid) are called in series. GC contains 21 series, including stop codons. In the following, for definiteness, any group of codons will be called liaison, if from each codon of this group you can go to all other codons of the same group by successive nucleotide substitutions. Of the 21 series, 18 are connected. 2 series contain one codon each, and only 1 series for the amino acid serine is unconnected and breaks up into two connected subseries.

Rice. 5. Connectivity graphs for some code series. a - connected series of valine; b - connected series of leucine; The serine series is incoherent and splits into two connected subseries. The figure is taken from the article by V.A. Ratner" Genetic code like a system."

The connectivity property can be explained by the fact that during the period of formation the GC captured new codons, which were minimally different from those already used.

9. Regularity properties of amino acids based on the roots of triplets. All amino acids encoded by triplets of the root U are non-polar, have no extreme properties and sizes, and have aliphatic radicals. All triplets with root C have strong bases, and the amino acids they encode are relatively small in size. All triplets with root A have weak bases and encode polar amino acids of no small size. Codons with a G root are characterized by extreme and anomalous variants of amino acids and series. They encode the smallest amino acid (glycine), the longest and flattest (tryptophan), the longest and gnarliest (arginine), the most reactive (cysteine), and form an anomalous subseries for serine.

10. Blockiness. The Universal Civil Code is a “block” code. This means that amino acids with similar physicochemical properties are encoded by codons that differ from each other by one base. The block nature of the code is clearly visible in the following figure.

Rice. 6. Block structure of the Civil Code. Amino acids with an alkyl group are indicated in white.

Rice. 7. Color representation of the physicochemical properties of amino acids, based on the values described in the bookStyers "Biochemistry". On the left is hydrophobicity. On the right is the ability to form an alpha helix in a protein. Red, yellow and blue colors indicate amino acids with high, medium and low hydrophobicity (left) or the corresponding degree of ability to form an alpha helix (right).

The property of blockiness and regularity can also be explained by the fact that during the period of formation the GC captured new codons, which were minimally different from those already used.

Codons with the same first bases (codon prefixes) encode amino acids with similar biosynthetic pathways. The codons of amino acids belonging to the shikimate, pyruvate, aspartate and glutamate families have U, G, A and C as prefixes, respectively. On the paths of ancient biosynthesis of amino acids and its connection with the properties of modern code, see "Ancient doublet genetic code was predetermined by the pathways of amino acid synthesis." Based on these data, some researchers conclude that the formation of the code was greatly influenced by the biosynthetic relationships between amino acids. However, the similarity of biosynthetic pathways does not at all mean the similarity of physicochemical properties.

11. Noise immunity. In the most general form, the noise immunity of HA means that with random point mutations and translation errors, the physicochemical properties of amino acids do not change very much.

Replacement of one nucleotide in a triplet in most cases either does not lead to a change in the encoded amino acid, or leads to a change to an amino acid with the same polarity.

One of the mechanisms that ensures the noise immunity of a GC is its degeneracy. The average degeneracy is equal to the number of encoded signals/total number of codons, where the encoded signals include 20 amino acids and the translation termination sign. The average degeneracy for all amino acids and the termination sign is three codons per encoded signal.

In order to quantify noise immunity, we introduce two concepts. Nucleotide substitution mutations that do not lead to a change in the class of the encoded amino acid are called conservative. Mutations of nucleotide substitutions leading to a change in the class of the encoded amino acid are called radical .

Each triplet allows 9 single substitutions. There are 61 amino acid-coding triplets in total. Therefore, the number of possible nucleotide substitutions for all codons is

61 x 9 = 549. Of these:

23 nucleotide substitutions result in stop codons.

134 substitutions do not change the encoded amino acid.
230 substitutions do not change the class of the encoded amino acid.
162 substitutions lead to a change in amino acid class, i.e. are radical.
Of the 183 substitutions of the 3rd nucleotide, 7 lead to the appearance of translation terminators, and 176 are conservative.
Of the 183 substitutions of the 1st nucleotide, 9 lead to the appearance of terminators, 114 are conservative and 60 are radical.
Of the 183 substitutions of the 2nd nucleotide, 7 lead to the appearance of terminators, 74 are conservative, 102 are radical.

Based on these calculations, we obtain a quantitative assessment of the noise immunity of the code as the ratio of the number of conservative replacements to the number of radical replacements. It is equal to 364/162=2.25

When realistically assessing the contribution of degeneracy to noise immunity, it is necessary to take into account the frequency of occurrence of amino acids in proteins, which varies in different species.

What is the reason for the noise immunity of the code? Most researchers believe that this property is a consequence of selection of alternative GCs.

Stephen Freeland and Lawrence Hurst generated random such codes and found that only one in a hundred alternative codes was no less noise-resistant than the universal code.
An even more interesting fact emerged when these researchers introduced an additional constraint to account for actual trends in DNA mutation patterns and translation errors. Under such conditions, ONLY ONE CODE OUT OF A MILLION POSSIBLE turned out to be better than the canonical code.
This unprecedented vitality of the genetic code can most easily be explained by the fact that it was formed as a result of natural selection. Perhaps there were once many codes in the biological world, each with its own sensitivity to errors. The organism that coped better with them had a greater chance of survival, and the canonical code simply won the struggle for existence. This assumption seems quite realistic - after all, we know that alternative codes really exist. For more information about noise immunity, see Coded evolution (S. Freeland, L. Hirst “Coded evolution”. // In the world of science. - 2004, No. 7).

In conclusion, I propose to count the number of possible genetic codes that can be generated for the 20 canonical amino acids. For some reason I didn’t come across this number anywhere. So, we need that the generated GCs must contain 20 amino acids and a stop signal, encoded by AT LEAST ONE CODON.

Let's mentally number the codons in some order. We will reason as follows. If we have exactly 21 codons, then each amino acid and stop signal will occupy exactly one codon. In this case, there will be 21 possible GCs!

If there are 22 codons, then an extra codon appears, which can have one of any 21 senses, and this codon can be located in any of the 22 places, while the remaining codons have exactly one different sense, as in the case of 21 codons. Then we get the number of combinations 21!x(21x22).

If there are 23 codons, then, reasoning similarly, we obtain that 21 codons have exactly one different meaning each (21! options), and two codons have 21 different meaning each (21 2 meanings with a FIXED position of these codons). The number of different positions for these two codons will be 23x22. The total number of GC variants for 23 codons is 21!x21 2 x23x22

If there are 24 codons, then the number of GCs will be 21!x21 3 x24x23x22,...

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