Mutagenesis induced by polynucleotides
A review of the modern condition of the problem ofmutagenesis by means of polynucleotides of natural and artifical origin. Peculiarities and regularities of their mutagene activity have been characterized. The received results give new information about the nature unstability of genes and the transp...
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Інститут молекулярної біології і генетики НАН України
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irk-123456789-1561942019-06-19T01:31:28Z Mutagenesis induced by polynucleotides Alexandrov, Yu.N. A review of the modern condition of the problem ofmutagenesis by means of polynucleotides of natural and artifical origin. Peculiarities and regularities of their mutagene activity have been characterized. The received results give new information about the nature unstability of genes and the transpositions regularity. The problem of mutagen activity of polynucleotides is being discussed in the field of the gypothesis of insertion mutagenesis. Зроблено огляд сучасного стану проблеми мутагенезу за допомогою полінуклеотидів природного і штучного походження. Охарактеризовано особливості і закономірності їх мутагенної дії. Отримані результати дають нові відомості щодо природи нестабільності генів і закономірностях їх транспозицій. Проблема мутагенної дії полінуклеотидів обговорюються в світлі гіпотези інсерційного мутагенезу. Сделан обзор современного состояния проблемы мутагенеза с помощью полинуклеотидов природного и искусственного происхождения. Охарактеризованы особенности и закономерности их мутагенного действия. Полученные результаты дают новые сведения о природе нестабильности генов и закономерностях их транспозиций. Проблема мутагенного действия полинуклеотидов обсуждаются в свете гипотезы инсерционного мутагенеза. 1995 Article Mutagenesis induced by polynucleotides / Yu.N. Alexandrov // Биополимеры и клетка. — 1995. — Т. 11, № 6. — С. 51-56. — Бібліогр.: 48 назв. — англ. 0233-7657 DOI: http://dx.doi.org/10.7124/bc.000403 http://dspace.nbuv.gov.ua/handle/123456789/156194 575.17 en Биополимеры и клетка Інститут молекулярної біології і генетики НАН України |
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A review of the modern condition of the problem ofmutagenesis by means of polynucleotides of natural and artifical origin. Peculiarities and regularities of their mutagene activity have been characterized. The received results give new information about the nature unstability of genes and the transpositions regularity. The problem of mutagen activity of polynucleotides is being discussed in the field of the gypothesis of insertion mutagenesis. |
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Alexandrov, Yu.N. |
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Alexandrov, Yu.N. Mutagenesis induced by polynucleotides Биополимеры и клетка |
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Alexandrov, Yu.N. |
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Alexandrov, Yu.N. |
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Mutagenesis induced by polynucleotides |
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Mutagenesis induced by polynucleotides |
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Mutagenesis induced by polynucleotides |
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Mutagenesis induced by polynucleotides |
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Mutagenesis induced by polynucleotides |
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mutagenesis induced by polynucleotides |
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Інститут молекулярної біології і генетики НАН України |
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1995 |
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Mutagenesis induced by polynucleotides / Yu.N. Alexandrov // Биополимеры и клетка. — 1995. — Т. 11, № 6. — С. 51-56. — Бібліогр.: 48 назв. — англ. |
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Биополимеры и клетка |
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AT alexandrovyun mutagenesisinducedbypolynucleotides |
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2025-07-14T08:33:51Z |
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2025-07-14T08:33:51Z |
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1837610610954600448 |
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ISSN 0233-7657. Биополимеры и клетка. 1995. Т. 11. № 6
UDC 575.17
Yu. N. Alexandre»'
Mutagenesis induced by polynucleotides
A review of the modern condition of the problem of mutagenesis by means of polynucleotides of natural and
artifical origin. Peculiarities and regularities of their mutagens activity have been characterized. The
received results give new information about the nature unstability of genes and the transpositions regularity.
The problem of mutagen activity of polynucleotides is being discussed in the field of the gypothesis of
insertion mutagenesis.
Fore more than a half of a century geneticists have carried out the artifical
mutagenes (x-rays, alkyl compounds and other chemical substances). They are
used now a rule only increase (sometimes substantially) the general frequency
of mutations but don't change radically their spectrum at least in eukaryots. In
other words, general frequency of mutations of different genes stays ap
proximately the same as without experimental interference. Genes that are
characterized by rather high frequency of spontaneous mutations change
especially often by usual use of mutagenic factors; but genes that have a low
ability to give natural mutations continue to mutate relatively less in the time
of influence of these mutagenes.
The remarkable discovery of the mutagenic effect of DNA [1] had
fundamental importance for subsequent genetic investigations. First, the role
which DNA can play in genetic processes was demonstrated; second, a strong
chemical mutagen, unlike the rather weak ones discovered earlier, was found
[2, 31; third, the obtainment of specific mutations was one of the most
important results. All these facts together promoted in the future the rapid
development of investigations in the area of chemical mutagenesis.
In the preface to his work, Gershenson indicated that the work was carried
out "on the basis of a number of theoretical considerations concerning the
nature of chromosomes, and also on the basis of facts obtained in recent years
with respect to the role played by nucleic acid in realizing hereditary
characters" [1 ].
Originally in investigations on mutagenesis experiments were set up by
means of one type of DNA — a preparation isolated from the calf thymus (mol.
wt. 0.5—1.0 million), which was mixed into the food of Drosophila larvae. The
methods used made it possible to detect visible recessive and dominant
mutations on the X chromosome, visible dominant mutations in autosomes, and
recessive lethal mutations in the X chromosome. It was found that preparations
of this DNA induce in Drosophila numerous sex-linked and autosomal visible
mutations and only an insignificant number of sex-linked lethals [4, 5] .
The main results obtained under the effect of DNA on Drosophila can be
formulated in the following way: the spectrum of induced mutations radically
differed from the spectrum of spontaneous mutations or mutations induced by
other chemical or physical mutagens; DNA induced point mutations, i. е., gene
mutations or microaberrations, but did not induce large chromosomal aberra
tions; DNA had a prolonged mutagenic effect, it induced mutations not only in
sex and somatic cells present at the time of injecting DNA into Drosophila, but
also in many subsequent generations; certain DNA-induced gene mutations
© Yu. N. ALBXANDROV, 1995
51
Уч. N. AJLEXANDROV
were unstable: they often reverted to the norm or passed into another allelic
state.
On the basis of these results, still at the dawn of development of
investigations in the area of chemical mutagenesis, Gershenson expressed ideas
at which molecular genetics arrive only 25 years later. He wrote: "Our
established fact ... should be interpreted as evidence in behalf of the fact that
a change in the part of the chromosome molecule consisting of DNA actually
can induce a gene mutation. ... The especially frequent mutation of certain
genes under the effect of our DNA preparation leads to the notion of a different
chemical structure of DNA of different gene molecules. So far we more or less
satisfactorily know the structure only of DNA from the calf thymus and it
simply cannot be ruled out that there exists numerous other DNAs having the
same carbohydrate (deoxyribose) and therefore producing the same Feulgen
reaction but differing in the character and arrangement of other parts. ... The
consequences of feeding (Drosophila) DNA can be explained most easily by the
assumption that the effect used disrupts the process of reproduction of genes,
as a result of which the newly formed genes sometimes differ in their structure
from the original ones.; If such an explanation is correct, it means that DNA
plays an important role in the reproduction of genes" [5].
Works on the induction of mutations by means of DNA in Drosophila
continued (with interruptions) and constantly gave the same surprising and
interesting results [6 ]. Subsequently, when the emphasis of investigations was
transferred from visible mutations to the obtainment of primarily lethal
mutations (mainly in the second chromosome) as an objectively recordable class
of pronounced alterations giving information on at least 80 % of the loci of the
genome and the injection of DNA preparations began to be used instead of
feeding, the main conclusions about the specific characteristics of the mutagenic
effect of DNA were confirmed and extended [7—11 ]. It was found that DNA
of different origins (more than 10 preparations with a molecular weight from 2
to 33 million isolated from animals, plants, and viruses were studied) induces
a limited number of repeatedly occurring lethal mutations, and the frequency
of mutations per locus reaches enormous values, exceeding by hundreds and
thousands of times the analogous frequency of mutations occurring under the
effect of various physical and chemical mutagens. The complementation test as
one of the most important criteria for establishing the selectivity of the effect
of mutagens revealed still another surprising property ot the mutagenic effect of
DNA preparations — complex allelic rations existed between chromosomes with
lethals. The sense of this phenomenon in the simplest case consisted in that two
chromosomes separately allelic to a third were not allelic to each other. Such
interrelations of defects induced in chromosomes could be explained by
transgressing deletions, interallelic complementation, and presence of lethals in
different loci of the chromosomes. Only the last assumption found experimental
confirmation of this interesting phenomenon. It was postulated by a mathe
matical analysis [12] and proved by direct experiment in which the comple
mentation data were compared with the data of a recombination analysis [13,
14]. According to the calculations, about 50 % of chromosomes in which lethal
mutations occur under the effect of exogenous DNA should be considered
multilethal. Thus the occurrence of multilethal chromosomes and the large
number of "allelic linkages" reflects still another important characteristic of the
mutagenic effect of exogenous DNAs.
It followed from the experiments on complementation and also in cases of
genetic mapping that each DNA preparation had, as a rule, its own charac
teristic spectrum of lethal mutations differing from the spectrum of DNA-
induced mutations from other organisms; however, these differences were not
absolute, and almost always loci of a common occurrence were found. Evidently,
52
MUTAGENESIS INDUCED BY POLYNUCLEOTIDES
the selectivity of the mutagenic effect of each of the investigated DNA
preparations was determined by two components. The main one is the
specificity of the effect of a given mutagen, and the second, having a
subordinate value, characterizes genes or segments of chromosomes especially
sensitive to the effect of these mutagens.
Experiments on a comparative study of the mutagenic activity of different
natural DNAs led, in addition to the aforementioned regularities, to a number
of interesting conclusions. The most important of them are as follows: 1) DNA
of a different species origin exhibits a different mutagenic activity; 2) the
specificity of the mutagenic effect of heterologous and homologous DNA is
different. Whereas as heterologous DNAs have, as a rule, a high intra-
chromosomal specificity, homologous DNA is characterized by the absence of
such; 3) cells of the premeiotic stage of gametogenesis of Drosophila are more
sensitive to the mutagenic effect of DNA; 4) DNA can induce direct mutations,
reversions, and transpositions [11, 15—20].
It is important to note that the mutagenic effect of DNA after the
fundamental works of Gershenson was established by a number of other
investigators working with Drosophila [21—30]. Numerous authors showed that
DNA is mutagenic also for other organisms — bacteria [31, 32] , blue-green
algae [33], fungi [34], higher plants [35], insects [36], and mammals [37,
38]. Thus the discovery of the mutagenic properties of exogenous DNA gained
complete recognition [39 ].
Gershenson's works on the mutagenic effect of DNA found their logical
continuation in a study of the mutagenic effect of viruses not infections for
Drosophila and artificially synthesized polynucleotides. It was found that only
the nucleic acid of viruses, but not their proteins, has^a mutagenic principle and,
as a consequence of this, a high selectivity of the mutagenic effect of viruses.
All unique properties which were characteristic of the preparations of exogenous
DNAs were demonstrated analogously in a study of mutagenesis by means of
viruses and high-polymer artificial polynucleotides [10, 40, 41 ].
The true nature of the mutagenic effect of DNA has still not been
completely explained, although since the time of the discovery of this
phenomenon more than 50 years have passed. It is now assumed than DNAs
induce mutations of the insertion type, being incorporated into genomes at
places of incomplete homology [42 ]. This is indicated both by indirect data on
a comparison of the characteristics of mutations induced by exogenous DNAs
and spontaneous insertion mutations in Drosophila [43] (locus specificity, high
total frequency of mutations and high frequency of mutations per locus, cluster
occurrence of mutations in the premeiotic stage of gametogenesis, instability)
and by recently conducted direct experiments to establish the sequences of
exogenous DNA in the Drosophila genome, for which this DNA was mutagenic
[44]. The prolonged effect of exogenous DNAs can be explained by the fact
that fragments of molecules (probably forming rings) injected into Drosophila
are present in the cytoplasm either in a free state and are transmitted from one
generation of cells to another or are inserted into the chromosome of the
recipient, causing gene mutations or microaberrations. The detected instabilities
of certain mutations are most probably caused by excision of the inserted
fragments of exogenous DNAs or by change in their orientation in the
chromosome. On the basis of this hypothesis the absence of mutagenic locus
specificity in homologous DNA becomes understandable. Fragments of this
DNA of Drosophila with respect to their physical characteristics and nucleotide
sequences correspond to a multitude of loci of Drosophila chromosomes,
whereas only few fragments of heterologous DNAs can have a random affinity
with the extremely limited number of loci.
The supposition was also expressed that polynucleotides of natural and
53
Yu N. ALEXANDROV
artificial origin injected into Drosophila could be another way to act on the
genome — by activation of its mobile element (MEs), which by their
translocations could cause mutations of certain genes [41]. The possibility of
such a way of inducing mutations by exogenous polynucleotides is indirectly
confirmed by the discovery of the phenomenon of so-called transposition
explosions, when it was possible to observe mass translocations of MEs
accompanied by multiple mutation events [45, 46]. The multilethal chromo
somes detected in experiments on mutagenesis by means of DNA, viruses, and
synthetic polynucleotides with the simultaneous occurrence of a large number
of mutations in them is the result of unique mutation "explosions", which
probably should be preceded by the "transposition explosions". If the inter
linked character of these events will be proved in the future, it will serve as still
another weighty argument in behalf of the insertion nature of the mutagenic
effect of exogenous polynucleotides, although in this case fragments of DNA of
an endogenous origin will be insertions.
Thus, generalization the aforesaid, we would like to emphasize once again
the important role of the discovery of the mutagenic effect of exogenous DNAs
— their high mutagenecity, selectivity of action, and nontoxicity [47, 48 ].
It is still premature to speak about the practical use of these substances on
a wide scale, nevertheless exogenous DNA was the first chemical substance
which engendered in geneticists the hope of inducing mutations of certain genes
in higher organisms, which would be of enormous value for practical breeding.
This gives possibility to hope that in the future by testing the mutagen
activity of different DNAs and especially artificial polynucleotides with the know
structure. It will also be possible to find the way in selected induction of
mutations that change phenotype into the definite side.
Ю. М. Александров
МУТАГЕНЕЗ, ІНДУКОВАНИЙ ПОЛШУКЛЕОТИДАМИ
Резюме
Зроблено огляд сучасного стану проблеми мутагенезу за допомогою полінуклеотидів природного
і штучного походження. Охарактеризовано особливості і закономірності їх мутагенної дії.
Отримані результати дають нові відомості щодо природи нестабільності генів і закономірностях
їх транспозицій. Проблема мутагенної дії полінуклеотидів обговорюються в світлі гіпотези
інсерційного мутагенезу
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Inst of Plant Physiol, and Genet. Received
Nat Acad, of Sci. of the Ukraine, Kyiv 12.05.95
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