What characteristic of the genetic code is the statement based on? The uniqueness of the genetic code is manifested in the fact that

The genetic code is usually understood as a system of signs indicating the sequential arrangement of nucleotide compounds in DNA and RNA, which corresponds to another sign system, displaying the sequence of amino acid compounds in a protein molecule.

This is important!

When scientists managed to study the properties genetic code, one of the main ones was recognized as versatility. Yes, strange as it may sound, everything is united by one, universal, common genetic code. It was formed over a long period of time, and the process ended about 3.5 billion years ago. Consequently, traces of its evolution can be traced in the structure of the code, from its inception to the present day.

When we talk about the sequence of arrangement of elements in the genetic code, we mean that it is far from chaotic, but strictly a certain order. And this also largely determines the properties of the genetic code. This is equivalent to the arrangement of letters and syllables in words. Once we break the usual order, most of what we read on the pages of books or newspapers will turn into ridiculous gobbledygook.

Basic properties of the genetic code

Usually the code contains some information encrypted in a special way. In order to decipher the code, you need to know distinctive features.

So, the main properties of the genetic code are:

• triplicity;
• degeneracy or redundancy;
• unambiguity;
• continuity;
• the versatility already mentioned above.

Let's take a closer look at each property.

1. Triplety

This is when three nucleotide compounds form a sequential chain within a molecule (i.e. DNA or RNA). As a result, a triplet compound is created or encodes one of the amino acids, its location in the peptide chain.

Codons (they are also code words!) are distinguished by their sequence of connections and by the type of those nitrogenous compounds (nucleotides) that are part of them.

In genetics, it is customary to distinguish 64 codon types. They can form combinations of four types 3 nucleotides each. This is equivalent to raising the number 4 to the third power. Thus, the formation of 64 nucleotide combinations is possible.

2. Redundancy of the genetic code

This property is observed when several codons are required to encrypt one amino acid, usually in the range of 2-6. And only tryptophan can be encoded using one triplet.

3. Unambiguity

It is included in the properties of the genetic code as an indicator of healthy genetic inheritance. For example, the GAA triplet, which is in sixth place in the chain, can tell doctors about the good state of the blood, about normal hemoglobin. It is he who carries information about hemoglobin, and it is also encoded by it. And if a person has anemia, one of the nucleotides is replaced by another letter of the code - U, which is a signal of the disease.

4. Continuity

When recording this property of the genetic code, it should be remembered that codons, like links in a chain, are located not at a distance, but in direct proximity, one after another in the nucleic acid chain, and this chain is not interrupted - it has no beginning or end.

5. Versatility

We should never forget that everything on Earth is united by a common genetic code. And therefore, in primates and humans, in insects and birds, in a hundred-year-old baobab tree and in a blade of grass that barely emerges from the ground, similar triplets encode similar amino acids.

It is in genes that the basic information about the properties of a particular organism is contained, a kind of program that the organism inherits from those who lived earlier and which exists as a genetic code.

In any cell and organism, all anatomical, morphological and functional features are determined by the structure of the proteins that comprise them. Hereditary property The body is able to synthesize certain proteins. Amino acids are located in a polypeptide chain, on which biological characteristics depend.
Each cell has its own sequence of nucleotides in the polynucleotide chain of DNA. This is the genetic code of DNA. Through it, information about the synthesis of certain proteins is recorded. About what the genetic code is, about its properties and genetic information is discussed in this article.

A little history

The idea that there might be a genetic code was formulated by J. Gamow and A. Down in the mid-twentieth century. They described that the nucleotide sequence responsible for the synthesis of a particular amino acid contains at least three units. Later they proved the exact number of three nucleotides (this is a unit of genetic code), which was called a triplet or codon. There are sixty-four nucleotides in total, because the acid molecule where RNA occurs is made up of four different nucleotide residues.

What is genetic code

The method of encoding the sequence of amino acid proteins due to the sequence of nucleotides is characteristic of all living cells and organisms. This is what the genetic code is.
There are four nucleotides in DNA:

• adenine - A;
• guanine - G;
• cytosine - C;
• thymine - T.

They are denoted by capital Latin or (in Russian-language literature) Russian letters.
RNA also contains four nucleotides, but one of them is different from DNA:

• adenine - A;
• guanine - G;
• cytosine - C;
• uracil - U.

All nucleotides are arranged in chains, with DNA having a double helix and RNA having a single helix.
Proteins are built on twenty amino acids, where they, located in a certain sequence, determine its biological properties.

Properties of the genetic code

Tripletity. A unit of genetic code consists of three letters, it is triplet. This means that the twenty amino acids that exist are encoded by three specific nucleotides called codons or trilpets. There are sixty-four combinations that can be created from four nucleotides. This amount is more than enough to encode twenty amino acids.
Degeneracy. Each amino acid corresponds to more than one codon, with the exception of methionine and tryptophan.
Unambiguity. One codon codes for one amino acid. For example, in the gene healthy person with information about the beta target of hemoglobin, the triplet of GAG and GAA encodes A in everyone with sickle cell disease, one nucleotide is changed.
Collinearity. The sequence of amino acids always corresponds to the sequence of nucleotides that the gene contains.
The genetic code is continuous and compact, which means that it has no punctuation marks. That is, starting at a certain codon, continuous reading occurs. For example, AUGGGUGTSUUAAUGUG will be read as: AUG, GUG, TSUU, AAU, GUG. But not AUG, UGG and so on or anything else.
Versatility. It is the same for absolutely all terrestrial organisms, from humans to fish, fungi and bacteria.

Table

Not all available amino acids are included in the table presented. Hydroxyproline, hydroxylysine, phosphoserine, iodine derivatives of tyrosine, cystine and some others are absent, since they are derivatives of other amino acids encoded by m-RNA and formed after modification of proteins as a result of translation.
From the properties of the genetic code it is known that one codon is capable of encoding one amino acid. The exception is the performer additional features and encoding valine and methionine, the genetic code. The mRNA, being at the beginning of the codon, attaches t-RNA, which carries formylmethione. Upon completion of the synthesis, it is cleaved off and takes the formyl residue with it, transforming into a methionine residue. Thus, the above codons are the initiators of the synthesis of the polypeptide chain. If they are not at the beginning, then they are no different from the others.

Genetic information

This concept means a program of properties that is passed down from ancestors. It is embedded in heredity as a genetic code.
The genetic code is realized during protein synthesis:

• messenger RNA;
• ribosomal rRNA.

Information is transmitted through direct communication (DNA-RNA-protein) and reverse communication (medium-protein-DNA).
Organisms can receive, store, transmit it and use it most effectively.
Passed on by inheritance, information determines the development of a particular organism. But due to interaction with the environment, the reaction of the latter is distorted, due to which evolution and development occur. In this way it is introduced into the body new information.

Computing patterns molecular biology and the discovery of the genetic code illustrated the need to combine genetics with Darwin's theory, on the basis of which a synthetic theory of evolution emerged - non-classical biology.
Darwin's heredity, variation and natural selection are complemented by genetically determined selection. Evolution is realized at the genetic level through random mutations and inheritance of the most valuable traits that are most adapted to environment.

Decoding the human code

In the nineties, the Human Genome Project was launched, as a result of which genome fragments containing 99.99% of human genes were discovered in the 2000s. Fragments that are not involved in protein synthesis and are not encoded remain unknown. Their role remains unknown for now.

Last discovered in 2006, chromosome 1 is the longest in the genome. More than three hundred and fifty diseases, including cancer, appear as a result of disorders and mutations in it.

The role of such studies cannot be overestimated. When they discovered what the genetic code is, it became known according to what patterns development occurs, how the morphological structure, psyche, predisposition to certain diseases, metabolism and defects of individuals are formed.

GENETIC CODE, recording system hereditary information in the form of a sequence of nucleotide bases in DNA molecules (in some viruses - RNA), which determines the primary structure (location of amino acid residues) in protein molecules (polypeptides). The problem of the genetic code was formulated after the proof genetic role DNA (American microbiologists O. Avery, K. McLeod, M. McCarthy, 1944) and deciphering its structure (J. Watson, F. Crick, 1953), after establishing that genes determine the structure and functions of enzymes (the “principle” one gene - one enzyme” by J. Beadle and E. Tatema, 1941) and that there is a dependence of the spatial structure and activity of a protein on its primary structure (F. Sanger, 1955). The question is how combinations of 4 bases nucleic acids determine the alternation of 20 common amino acid residues in polypeptides, first stated by G. Gamow in 1954.

Based on an experiment in which they studied the interactions of insertions and deletions of a pair of nucleotides, in one of the genes of the T4 bacteriophage, F. Crick and other scientists in 1961 determined general properties genetic code: triplet, i.e. each amino acid residue in the polypeptide chain corresponds to a set of three bases (triplet, or codon) in the DNA of the gene; codons within a gene are read from a fixed point, in one direction and “without commas”, that is, the codons are not separated by any signs from each other; degeneracy, or redundancy - the same amino acid residue can be encoded by several codons (synonymous codons). The authors assumed that the codons do not overlap (each base belongs to only one codon). Direct study of the coding ability of triplets was continued using a cell-free protein synthesis system under the control of synthetic messenger RNA(mRNA). By 1965, the genetic code was completely deciphered in the works of S. Ochoa, M. Nirenberg and H. G. Korana. Unraveling the secret of the genetic code was one of the outstanding achievements biology in the 20th century.

The implementation of the genetic code in a cell occurs during two matrix processes - transcription and translation. The mediator between the gene and the protein is mRNA, which is formed during transcription on one of the DNA strands. In this case, the sequence of DNA bases, carrying information about the primary structure of the protein is “rewritten” as a sequence of mRNA bases. Then, during translation on ribosomes, the nucleotide sequence of the mRNA is read by transfer RNAs (tRNAs). The latter have an acceptor end, to which an amino acid residue is attached, and an adapter end, or anticodon triplet, which recognizes the corresponding mRNA codon. The interaction of a codon and an anti-codon occurs on the basis of complementary base pairing: Adenine (A) - Uracil (U), Guanine (G) - Cytosine (C); in this case, the base sequence of the mRNA is translated into the amino acid sequence of the synthesized protein. Various organisms They use different synonymous codons with different frequencies for the same amino acid. Reading of the mRNA encoding the polypeptide chain begins (initiates) with the AUG codon corresponding to the amino acid methionine. Less commonly, in prokaryotes, the initiation codons are GUG (valine), UUG (leucine), AUU (isoleucine), and in eukaryotes - UUG (leucine), AUA (isoleucine), ACG (threonine), CUG (leucine). This sets the so-called frame, or phase, of reading during translation, that is, then the entire nucleotide sequence of the mRNA is read triplet by triplet of tRNA until any of the three terminator codons, often called stop codons, are encountered on the mRNA: UAA, UAG , UGA (table). Reading of these triplets leads to the completion of the synthesis of the polypeptide chain.

AUG and stop codons appear at the beginning and end of the mRNA regions encoding polypeptides, respectively.

The genetic code is quasi-universal. This means that there are slight variations in the meaning of some codons between objects, and this applies primarily to terminator codons, which can be significant; for example, in the mitochondria of some eukaryotes and mycoplasmas, UGA encodes tryptophan. In addition, in some mRNAs of bacteria and eukaryotes, UGA encodes an unusual amino acid - selenocysteine, and UAG in one of the archaebacteria - pyrrolysine.

There is a point of view according to which the genetic code arose by chance (the “frozen chance” hypothesis). It's more likely that it evolved. This assumption is supported by the existence of a simpler and, apparently, more ancient version of the code, which is read in mitochondria according to the “two out of three” rule, when the amino acid is determined by only two of the three bases in the triplet.

Lit.: Crick F. N. a. O. General nature of the genetic code for proteins // Nature. 1961. Vol. 192; The genetic code. N.Y., 1966; Ichas M. Biological code. M., 1971; Inge-Vechtomov S.G. How the genetic code is read: rules and exceptions // Modern natural science. M., 2000. T. 8; Ratner V. A. Genetic code as a system // Soros educational journal. 2000. T. 6. No. 3.

S. G. Inge-Vechtomov.

The genetic code, expressed in codons, is a system for encoding information about the structure of proteins, inherent in all living organisms on the planet. It took a decade to decipher it, but science understood that it existed for almost a century. Universality, specificity, unidirectionality, and especially the degeneracy of the genetic code are important biological significance.

History of discoveries

The problem of coding has always been key in biology. Science has moved rather slowly towards the matrix structure of the genetic code. Since the discovery of the double helical structure of DNA by J. Watson and F. Crick in 1953, the stage of unraveling the very structure of the code began, which prompted faith in the greatness of nature. The linear structure of proteins and the same structure of DNA implied the presence of a genetic code as a correspondence between two texts, but written using different alphabets. And if the alphabet of proteins was known, then the signs of DNA became the subject of study by biologists, physicists and mathematicians.

There is no point in describing all the steps in solving this riddle. A direct experiment that proved and confirmed that there is a clear and consistent correspondence between DNA codons and protein amino acids was carried out in 1964 by C. Janowski and S. Brenner. And then - the period of deciphering the genetic code in vitro (in a test tube) using protein synthesis techniques in cell-free structures.

The fully deciphered code of E. Coli was made public in 1966 at a symposium of biologists in Cold Spring Harbor (USA). Then the redundancy (degeneracy) of the genetic code was discovered. What this means is explained quite simply.

Decoding continues

Obtaining data on deciphering the hereditary code was one of the most significant events of the last century. Today, science continues to in-depth study the mechanisms of molecular encodings and its systemic features and excess of signs, which expresses the degeneracy property of the genetic code. A separate branch of study is the emergence and evolution of the system for coding hereditary material. Evidence of the connection between polynucleotides (DNA) and polypeptides (proteins) gave impetus to the development of molecular biology. And that, in turn, to biotechnology, bioengineering, discoveries in breeding and plant growing.

Dogmas and rules

The main dogma of molecular biology is that information is transferred from DNA to messenger RNA, and then from it to protein. In the opposite direction, transfer is possible from RNA to DNA and from RNA to another RNA.

But the matrix or basis always remains DNA. And all other fundamental features of information transmission are a reflection of this matrix nature of transmission. Namely, transmission through the synthesis of other molecules on the matrix, which will become the structure for the reproduction of hereditary information.

Genetic code

Linear coding of the structure of protein molecules is carried out using complementary codons (triplets) of nucleotides, of which there are only 4 (adeine, guanine, cytosine, thymine (uracil)), which spontaneously leads to the formation of another chain of nucleotides. The same number and chemical complementarity of nucleotides is the main condition for such a synthesis. But when a protein molecule is formed, there is no quality match between the quantity and quality of monomers (DNA nucleotides are protein amino acids). This is the natural hereditary code - a system for recording the sequence of amino acids in a protein in a sequence of nucleotides (codons).

The genetic code has several properties:

• Tripletity.
• Unambiguity.
• Directionality.
• Non-overlapping.
• Redundancy (degeneracy) of the genetic code.
• Versatility.

Let's give brief description, focusing on biological significance.

Triplety, continuity and the presence of stop signals

Each of the 61 amino acids corresponds to one sense triplet (triplet) of nucleotides. Three triplets do not carry amino acid information and are stop codons. Each nucleotide in the chain is part of a triplet and does not exist on its own. At the end and at the beginning of the chain of nucleotides responsible for one protein, there are stop codons. They start or stop translation (the synthesis of a protein molecule).

Specificity, non-overlap and unidirectionality

Each codon (triplet) codes for only one amino acid. Each triplet is independent of its neighbor and does not overlap. One nucleotide can be included in only one triplet in the chain. Protein synthesis always occurs in only one direction, which is regulated by stop codons.

Redundancy of the genetic code

Each triplet of nucleotides codes for one amino acid. There are 64 nucleotides in total, of which 61 encode amino acids (sense codons), and three are nonsense, that is, they do not encode an amino acid (stop codons). The redundancy (degeneracy) of the genetic code lies in the fact that in each triplet substitutions can be made - radical (lead to the replacement of an amino acid) and conservative (do not change the class of the amino acid). It is easy to calculate that if 9 substitutions can be made in a triplet (positions 1, 2 and 3), each nucleotide can be replaced by 4 - 1 = 3 other options, then total quantity possible options nucleotide substitutions will be 61 by 9 = 549.

The degeneracy of the genetic code is manifested in the fact that 549 variants are much more than are needed to encode information about 21 amino acids. Moreover, out of 549 variants, 23 substitutions will lead to the formation of stop codons, 134 + 230 substitutions are conservative, and 162 substitutions are radical.

Rule of degeneracy and exclusion

If two codons have two identical first nucleotides, and the remaining ones are represented by nucleotides of the same class (purine or pyrimidine), then they carry information about the same amino acid. This is the rule of degeneracy or redundancy of the genetic code. Two exceptions are AUA and UGA - the first encodes methionine, although it should be isoleucine, and the second is a stop codon, although it should encode tryptophan.

The meaning of degeneracy and universality

It is these two properties of the genetic code that have the greatest biological significance. All the properties listed above are characteristic of the hereditary information of all forms of living organisms on our planet.

The degeneracy of the genetic code has adaptive significance, like multiple duplication of the code for one amino acid. In addition, this means a decrease in significance (degeneration) of the third nucleotide in the codon. This option minimizes mutational damage in DNA, which will lead to gross violations in the protein structure. This defense mechanism living organisms on the planet.

Ministry of Education and Science Russian Federation Federal agency by education

State educational institution higher vocational education"Altai State technical university them. I.I. Polzunov"

Department of Natural Sciences and System Analysis

Abstract on the topic "Genetic code"

1. The concept of genetic code

3. Genetic information

References

1. The concept of genetic code

Genetic code - characteristic of living organisms unified system recording hereditary information in nucleic acid molecules in the form of a sequence of nucleotides. Each nucleotide is designated by a capital letter, which begins the name of the nitrogenous base included in its composition: - A (A) adenine; - G (G) guanine; - C (C) cytosine; - T (T) thymine (in DNA) or U (U) uracil (in mRNA).

The implementation of the genetic code in a cell occurs in two stages: transcription and translation.

The first of them occurs in the core; it consists in the synthesis of mRNA molecules at the corresponding sections of DNA. In this case, the DNA nucleotide sequence is “rewritten” into the RNA nucleotide sequence. The second stage takes place in the cytoplasm, on ribosomes; in this case, the sequence of nucleotides of the mRNA is translated into the sequence of amino acids in the protein: this stage occurs with the participation of transfer RNA (tRNA) and the corresponding enzymes.

2. Properties of the genetic code

1. Triplety

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

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 by 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 amino acids of 1 triplet = 2 9 amino acids of 2 triplets = 18 1 amino acid 3 triplets = 3 5 amino acids of 4 triplets = 20 3 amino acids of 6 triplets = 18 Total 61 triplets encode 20 amino acids.

3. Presence of intergenic punctuation marks.

A gene is a section of DNA that encodes one polypeptide chain or one molecule of tRNA, rRNA or sRNA.

The tRNA, rRNA, and sRNA genes do not code for proteins.

At the end of each gene encoding a polypeptide there is at least one of 3 stop codons, or stop signals: UAA, UAG, UGA. They terminate the broadcast.

Conventionally, the AUG codon, the first after the leader sequence, also belongs to punctuation marks. 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 AUG codon. 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 triplet and there are no punctuation marks inside the gene. The experiment was carried out on two adjacent phage genes and showed, in addition, the presence of punctuation marks between the genes.

3. Genetic information

Genetic information is a program of the properties of an organism, received from ancestors and embedded in hereditary structures in the form of a genetic code.

It is assumed that the formation of genetic information followed the following scheme: geochemical processes - mineral formation - evolutionary catalysis (autocatalysis).

It is possible that the first primitive genes were microcrystalline clay crystals, and each new layer of clay is built in accordance with the structural features of the previous one, as if receiving information about the structure from it.

The implementation of genetic information occurs in the process of synthesis of protein molecules using three RNAs: messenger RNA (mRNA), transport RNA (tRNA) and ribosomal RNA (rRNA). The process of information transfer occurs: - through a direct communication channel: DNA - RNA - protein; and - through the channel feedback: environment - protein - DNA.

Living organisms are capable of receiving, storing and transmitting information. Moreover, living organisms have an inherent desire to use the information received about themselves and the world around them as efficiently as possible. Hereditary information embedded in genes and necessary for a living organism to exist, develop and reproduce is transmitted from each individual to his descendants. This information determines the direction of development of the organism, and in the process of its interaction with the environment, the reaction to its individual can be distorted, thereby ensuring the evolution of the development of descendants. In the process of evolution of a living organism, new information arises and is remembered, including the value of information for it increases.

During the implementation of hereditary information under certain conditions external environment the phenotype of organisms of a given biological species is formed.

Genetic information determines the morphological structure, growth, development, metabolism, mental makeup, predisposition to diseases and genetic defects of the body.

Many scientists, rightly emphasizing the role of information in the formation and evolution of living things, noted this circumstance as one of the main criteria of life. So, V.I. Karagodin believes: “Living is such a form of existence of information and the structures encoded by it, which ensures the reproduction of this information in suitable environmental conditions.” The connection between information and life is also noted by A.A. Lyapunov: “Life is a highly ordered state of matter that uses information encoded by the states of individual molecules to develop conserved reactions.” Our famous astrophysicist N.S. Kardashev also emphasizes the informational component of life: “Life arises thanks to the possibility of synthesizing a special kind of molecules capable of remembering and using at first the most simple information about the environment and their own structure, which they use for self-preservation, for reproduction and, most importantly for us, for obtaining more more information." Ecologist F. Tipler draws attention to this ability of living organisms to preserve and transmit information in his book "Physics of Immortality": "I define life as a kind of encoded information that is preserved by natural selection." Moreover, he believes that if this is so , then the life-information system is eternal, infinite and immortal.

The discovery of the genetic code and the establishment of the laws of molecular biology showed the need to combine modern genetics and Darwinian theory of evolution. Thus was born a new biological paradigm - the synthetic theory of evolution (STE), which can already be considered as non-classical biology.

The basic ideas of Darwin's evolution with its triad - heredity, variability, natural selection - in the modern understanding of the evolution of the living world are complemented by the ideas of not just natural selection, but a selection that is determined genetically. The work of S.S. can be considered the beginning of the development of synthetic or general evolution. Chetverikov on population genetics, in which it was shown that it is not individual characteristics and individuals that are subject to selection, but the genotype of the entire population, but it is carried out through the phenotypic characteristics of individual individuals. This causes beneficial changes to spread throughout the population. Thus, the mechanism of evolution is realized both through random mutations at the genetic level and through the inheritance of the most valuable traits (the value of information!), which determine the adaptation of mutational traits to the environment, ensuring the most viable offspring.

Seasonal climate changes, various natural or man-made disasters on the one hand, they lead to a change in the frequency of gene repetition in populations and, as a consequence, to a decrease in hereditary variability. This process is sometimes called genetic drift. And on the other hand, to changes in the concentration of various mutations and a decrease in the diversity of genotypes contained in the population, which can lead to changes in the direction and intensity of selection.

4. Decoding the human genetic code

In May 2006, scientists working to decipher the human genome published a complete genetic map of chromosome 1, which was the last human chromosome not fully sequenced.

A preliminary human genetic map was published in 2003, marking the formal completion of the Human Genome Project. Within its framework, genome fragments containing 99% of human genes were sequenced. The accuracy of gene identification was 99.99%. However, by the time the project was completed, only four of the 24 chromosomes had been completely sequenced. The fact is that in addition to genes, chromosomes contain fragments that do not encode any characteristics and are not involved in protein synthesis. The role that these fragments play in the life of the body remains unknown, but more and more researchers are inclined to believe that their study requires the closest attention.