The epigene hypothesis
The possibility of storing hereditary information outside DNA genome molecules is discussed. A hypothesis of epigene as a unit is put forward. According to this hypothesis: a) hereditary information is coded for not only by the sequences of DNA nucleotides, but also by other means such as the presen...
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Інститут молекулярної біології і генетики НАН України
1997
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Tchuraev, R.N. 2019-06-15T17:26:10Z 2019-06-15T17:26:10Z 1997 The epigene hypothesis / R.N. Tchuraev // Биополимеры и клетка. — 1997. — Т. 13, № 1. — С. 75-81. — Бібліогр.: 13 назв. — англ. 0233-7657 DOI: http://dx.doi.org/10.7124/bc.00046B https://nasplib.isofts.kiev.ua/handle/123456789/154655 575.17 The possibility of storing hereditary information outside DNA genome molecules is discussed. A hypothesis of epigene as a unit is put forward. According to this hypothesis: a) hereditary information is coded for not only by the sequences of DNA nucleotides, but also by other means such as the presence or absence of some regulatory proteins; b) storage of hereditary information during the cell life cycle is provided by the feedback mechanism; c) the information inherited from parents to offspring is transmitted through the distribution of extragenomic macromolecules of regulatory substances. Models of the simplest systems with epigenic properties are considered. Depending on the concrete state of epigenes observed in different states and individual ontogenetic patterns, intercrosses may produce the following effects: 1) absorption (offspring will have epigenes in similar states; 2) formation of epiheterozygotes yielding gametes of various kinds; 3) formation of variants each reproducing gametes of only one kind and the variants producing different kinds of gametes. To detect epigenic effects the special interbreeding experiments are suggested. Запропоновано гіпотезу про епіген – одиницю, у якій: а) спадкова інформація кодується не лише послідовностями основ у молекулах ДНК, але й іншим способом, наприклад, присутністю або відсутністю визначених регуляторних білків; б) зберігання спадкової інформації протягом життя клітини забезпечується наявністю зворотних зв'язків; в) передача спадкової інформації від батьківської особини до нащадків здійснюється шляхом розподілу позагеномних макромолекул регулюючих речовин. Розглянуто моделі найпростіших систем з ознаками епігена. При схрещуванні особин, що містять епіген у різних станах в залежності від конкретного виду епігена та особливостей онтогенезу, у потомстві від схрещувань можуть статися наступні події: поглинання (нащадки матимуть епігени в однакових станах); 2) виникнення епігетерозиготи, яка дає гамлети різних сортів; 3) формування таких особин, кожна з яких виробляє лише один сорт гамет, але різні особини здатні виробляти різні сорти гамет. Запропоновано ідею експеримента, що дозволяє виявити епігени шляхом схрещування. Предложена гипотеза об эпигене – единице, в которой: а) наследственная информация кодируется не только последовательностью оснований в молекулах ДНК, но и другим способом, например, присутствием или отсутствием определенных регуляторних белков; б) хранение наследственной информации в течение жизни клетки обеспечивается наличием обратных связей; в) передача наследуемой информации от родительской особи к потомству происходит путем распределения вне геномных макромолекул регулирующих веществ. Рассмотрены модели простейших систем, обладающих свойствами эпигена. При скрещивании особей, содержащих эпигены в разных состояниях в зависимости от конкретного вида эпигена и особенностей онтогенеза, в потомстве от скрещиваний могут произойти следующие события): 1) поглощение (потомство будет иметь эпигены в одинаковых состояниях; 2) образование эпигетерозиготы, дающей гамлеты разных сортов; 3) образование таких особей, каждая из которых производит лишь один сорт гамет, но разные особи могут производить разные сорта гамет. Предложена идея эксперимента, позволяющего выявить эпигены путем скрещиваний. I am thankful to D. K. Belyaev, M. D. Golubovski, E. V. Gruntenko, L. L Korochkin, V. A. Kulichkov, Z. S. Nikoro, V. A. Ratner and V. V. Khvostova for their constructive discussion and valuable criticism, of the paper and I acknowledge the technical aid rendered by G. Kh. Ziganshina and I. G. Migranova. en Інститут молекулярної біології і генетики НАН України Биополимеры и клетка Геном и его регуляция The epigene hypothesis Гіпотеза про епіген Гипотеза об эпигене Article published earlier |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine |
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DSpace DC |
| title |
The epigene hypothesis |
| spellingShingle |
The epigene hypothesis Tchuraev, R.N. Геном и его регуляция |
| title_short |
The epigene hypothesis |
| title_full |
The epigene hypothesis |
| title_fullStr |
The epigene hypothesis |
| title_full_unstemmed |
The epigene hypothesis |
| title_sort |
epigene hypothesis |
| author |
Tchuraev, R.N. |
| author_facet |
Tchuraev, R.N. |
| topic |
Геном и его регуляция |
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Геном и его регуляция |
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1997 |
| language |
English |
| container_title |
Биополимеры и клетка |
| publisher |
Інститут молекулярної біології і генетики НАН України |
| format |
Article |
| title_alt |
Гіпотеза про епіген Гипотеза об эпигене |
| description |
The possibility of storing hereditary information outside DNA genome molecules is discussed. A hypothesis of epigene as a unit is put forward. According to this hypothesis: a) hereditary information is coded for not only by the sequences of DNA nucleotides, but also by other means such as the presence or absence of some regulatory proteins; b) storage of hereditary information during the cell life cycle is provided by the feedback mechanism; c) the information inherited from parents to offspring is transmitted through the distribution of extragenomic macromolecules of regulatory substances. Models of the simplest systems with epigenic properties are considered. Depending on the concrete state of epigenes observed in different states and individual ontogenetic patterns, intercrosses may produce the following effects: 1) absorption (offspring will have epigenes in similar states; 2) formation of epiheterozygotes yielding gametes of various kinds; 3) formation of variants each reproducing gametes of only one kind and the variants producing different kinds of gametes. To detect epigenic effects the special interbreeding experiments are suggested.
Запропоновано гіпотезу про епіген – одиницю, у якій: а) спадкова інформація кодується не лише послідовностями основ у молекулах ДНК, але й іншим способом, наприклад, присутністю або відсутністю визначених регуляторних білків; б) зберігання спадкової інформації протягом життя клітини забезпечується наявністю зворотних зв'язків; в) передача спадкової інформації від батьківської особини до нащадків здійснюється шляхом розподілу позагеномних макромолекул регулюючих речовин. Розглянуто моделі найпростіших систем з ознаками епігена. При схрещуванні особин, що містять епіген у різних станах в залежності від конкретного виду епігена та особливостей онтогенезу, у потомстві від схрещувань можуть статися наступні події: поглинання (нащадки матимуть епігени в однакових станах); 2) виникнення епігетерозиготи, яка дає гамлети різних сортів; 3) формування таких особин, кожна з яких виробляє лише один сорт гамет, але різні особини здатні виробляти різні сорти гамет. Запропоновано ідею експеримента, що дозволяє виявити епігени шляхом схрещування.
Предложена гипотеза об эпигене – единице, в которой: а) наследственная информация кодируется не только последовательностью оснований в молекулах ДНК, но и другим способом, например, присутствием или отсутствием определенных регуляторних белков; б) хранение наследственной информации в течение жизни клетки обеспечивается наличием обратных связей; в) передача наследуемой информации от родительской особи к потомству происходит путем распределения вне геномных макромолекул регулирующих веществ. Рассмотрены модели простейших систем, обладающих свойствами эпигена. При скрещивании особей, содержащих эпигены в разных состояниях в зависимости от конкретного вида эпигена и особенностей онтогенеза, в потомстве от скрещиваний могут произойти следующие события): 1) поглощение (потомство будет иметь эпигены в одинаковых состояниях; 2) образование эпигетерозиготы, дающей гамлеты разных сортов; 3) образование таких особей, каждая из которых производит лишь один сорт гамет, но разные особи могут производить разные сорта гамет. Предложена идея эксперимента, позволяющего выявить эпигены путем скрещиваний.
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0233-7657 |
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https://nasplib.isofts.kiev.ua/handle/123456789/154655 |
| citation_txt |
The epigene hypothesis / R.N. Tchuraev // Биополимеры и клетка. — 1997. — Т. 13, № 1. — С. 75-81. — Бібліогр.: 13 назв. — англ. |
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ISSN 0233-7657. Биополимеры и клетка. 1997. Т. 13. № 1
ГЕНОМ И ЕГО РЕГУЛЯЦИЯ
The epigene hypothesis
Rustem N. Tchuraev
Institute Biology Ufa Science Centre of the Academy of Science of the Russia
69 Prospect Octyabrya, Ufa 450054 , Russia
The possibility of storing hereditary information outside DNA genome molecules is discussed. A hypothesis
of epigene as a unit is put forward. According to this hypothesis: a) hereditary information is coded for
not only by the sequences of DNA nucleotides, but also by other means such as the presence or absence of
some regulatory proteins; b) storage of hereditary information during the cell life cycle is provided by the
feedback mechanism; c) the information inherited from parents to offspring is transmitted through the
distribution of extragenomic macromolecules of regulatory substances. Models of the simplest systems with
epigenic properties are considered. Depending on the concrete state of epigenes observed in different states
and individual ontogenetic patterns, intercrosses may produce the following effects: 1) absorption (offspring
will have epigenes in similar states; 2) formation of epiheterozygotes yielding gametes of various kinds; 3)
formation of variants each reproducing gametes of only one kind and the variants producing different kinds
of gametes. To detect epigenic effects the special interbreeding experiments are suggested.
One of the basic suggestions of modern molecular
biology is the concept that hereditary information is
encoded by nucleotide sequences of DNA genome
molecules. However, this does not rule out the
possibility of other ways of coding and storing here
ditary information. It is generally accepted that
information may be stored either by maintaining a
definite distribution pattern of elements of spatial
structure {structural way) or by circulation of signals
in the cyclic system of elements (dynamic way). In
DNA molecules information is stored by a structural
way. This paper is concerned with discussion of the
possibility of storing a part of hereditary information
by the dynamic way, outside DNA molecules. It
should be noted that DNA molecules code for the
structure of dynamic devices responsible for storing
information.
The term «structural gene» will imply a bound
part of DNA molecule coding for the structure of a
certain protein or RNA. Some genes may be either in
the active or non-active state differing in the intensity
of mRNA synthesis. Genes can form systems by
means of regulatory proteins. Of special interest are
cyclic gene systems having at least two functional
states and capable of maintaining each state both
during the cell life cycle and successive cellular
divisions.
© R. N. TCHURAEV, 1997
Such systems really exist. An illustrative case of
the cyclic system of this kind is the two-operon
molecular trigger in A-phage (Fig. 1) [1—31. This
system has two stable states: the first — operon L, is
switched on, R] is switched off; the second state —
operon R{ is switched on, Lx is switched off. The first
state of the system corresponds to the immune
(lysogenic) state of prophage when there is suppres
sion of the lytic growth of phage genomes penetrating
anew into the bacterial cell of the same prophage
strain. The second state of the system corresponds to
the nonimmune (lytic) state of the prophage when
reduplication of superinfected phage genomes is possi
ble. The first of these states is maintained both
during the host cell life and its successive divisions.
In the lytic state the phage undergoes a number of
successive reduplication cycles. This system presents
an example of a especially here — ditary unit, wherein
the genome is responsible only for the possibility of a
system being in one of the inheritable states, while
the concrete state of the initial prophage and daughter
phage genomes is determined by the presence or
absence of the respective repressor [1, 4] .
Epigene will be defined as a hereditary unit
(cyclic system) responsible for the activity of the
respective gene (or genes) and having at least two
alternative states which may be maintained in a
successive number of generations. Moreover, the tran
sition from one state to another is not necessarily
75
RUSTEM N. TCHURAEV
Fig. 1. Molecular trigger of the Л-phage. Protein products of genes Fig. 2. One-component model of epigene: A — structural gene; Cr —
C\ and to/are repressors for scriptons R\ and respectively. Only the gene-regulator, coding the protein-activator
first zone of the scripton R{ is depicted
accompanied by a change of the DNA structure, while
maintenance of each state is the system property. If
the system passes from one state to another due to
some exterior factors, the state the system has passed
to is maintained also after these factors cease affec
ting it. The existence of epigenes in prokaryotes does
not raise any doubts. The illustrative case is two-
operon trigger systems in lambdoid phages. We shall
consider the possibility of existence of epigenes in
eukaryotes. In this case, some genes of a multicellular
organism should be subordinated to systems (that is,
they are either embodied by these systems or connec
ted with them via direct bonds) capable of main
taining whether an active or inactive state through
successive cell divisions and formation of offspring in
a successive generation. It should be emphasized that
the choice of the system state must not be determined
(directly or indirectly) by genes embodied by these
systems.
Let us analyse the simplest systems possessing
the properties of epigenes which will serve an illust
ration of some inferences drawn from the hypothesis
of the existence of epigenes.
One-Component Model. Let us firstly consider
the simplest cyclic system composed of one trans
cription unit — a scripton (Fig. 2). A scripton is
assumed to contain a receptor zone having an affinity
for regulatory proteins (i. e. it is an operon), one or
several structural genes and a regulatory gene produ
cing a stable protein activator of the transcription of
the same operon. At sub threshold concentrations of
the activator, no effective transcription occurs; at
concentrations higher than threshold, it does occur.
Such a system has two alternative states. Each state
is preserved during cell life and transmitted to
daughter cells through successive divisions when the
state of the daughter cell system is determined by the
presence or absence of the activator protein in the
parental cell, that is, by the state of the parental cell
system. In this case, the succession or «inheritance»
of the system state is provided by the transfer of
activator proteins from the parental to daughter cells,
wherein they induce transcription of the scripton.
Such one-component model has a real prototype. The
protein C, of A-phage activates transcription of the
operon containing the cistron C, [5 ].
Eukaryotes possess some essential features which
may affect the capacity of cyclic systems to be
epigenes. The inheritance of system state in euka
ryotes includes the inheritance through cell lines, that
is, through mitoses and gametes. In the latter case,
each state of the system should be preserved during
meiosis, gametic stage, fertilization and early stages
of embryogenesis.
The inheritance of the active state through cell
lines is provided by the production of activator
proteins during each cell cycle and their distribution
among daughter cells. In the case of gametogenesis,
the situation is more complex.
During gametogenesis and at the early stages of
embryogenesis, many loci may be completely repres
sed (for example, as a result of chromosome coiling).
In the case of one-component model, this will not
affect the maintenance of the inactive state. As for the
alternative state, activator proteins and the respective
mRNAs will be kept diluted with each cell cycle. For
this reason, inheritance of the active state is possible
only when transcription and translation are turned off
for a period of time not exceeding that of the total
dilution of activator proteins. An important feature of
eukaryotes is the existence of very stable mRNAs [6 ].
The translation of such mRNAs can take place even
when there is no transcription at the respective loci.
Hence, if the epigene contains a stable mRNA the
76
THE EPIGENE HYPOTHESIS
period of dilution of activator proteins in the absence
of transcription may be sufficiently protracted. In
general, transcription and translation are perhaps not
altogether effaced during gametogenesis and early
embryogenesis [6]. Maintenance of the state of epi
genes which are not turned off by systems of a
hierarchically higher level, occurs the same way as in
the case of inheritance through cell lines.
Most eukaryotes are diploids, and in diploid cells
genes form pairs. We assume that the homologous
genes included in epigenes do not differ structurally,
that is, the organism is homozygous for these genes.
The state of a gene, included in the epigene, will be
designated by a binary upper index next to the gene
symbol. Thus, A1 will stand for the active state of the
gene A and A0 will refer to its inactive state. The term
«epigenotype» will denote a list of all the genes
included in an epigene with an indication of their
states. Organisms, of the same genotype may have
different epigenotypes. Thus, in the case of one-
component model, individuals with genotype AIA may
have epigenotypes Al/A] and A0/A0. This means that
in all the cells of the organism the gene A has either
an active (with the first epigenotype) or inactive (with
the second epigenotype) state. These individuals
produce gametes of one kind, A1 or A0. The more
complicated cases will be considered below. Pheno-
typically, individuals with the epigenotype A0/A0 will
look as a recessive homozygote while individuals with
the epigenotype A1 /A] — as a dominant homozygote.
Let us examine crosses between individuals,
taking into account their epigenotype.
LA°/A0xA0/A0-^A°/A0.
The partners form gametes containing no acti
vator proteins.
2. A1/A1 *Al/Al-^Al/A\
In this case activator proteins from gametes will
enter into a zygote.
3.Al/Al xA°/A°—»Al/Al.
In the latter case, due to the free migration of the
activator, the inactive epigene will pass into an active
state.
Phenotypically, this will appear as a transition of
one allele into another. This unification of epigene
states will be called absorption. The absorbed «hyb-
rids» of the first generation will produce gametes of
the same kind, and epigenotype А /А0 will not appear
in subsequent crosses, that is, segregation does not
occur.
As a result of the inconsiderable content of
cytoplasm in a male gamete, its capabilities to transfer
activator proteins are limited. The capacity to trans
mit an active state through a male gamete depends on
the effectiveness of activator proteins. If the affinity
of activator proteins for the respective receptor zones
is as strong as in the case of some regulatory
molecules in bacteria [7], a small amount of the
activators passed from the male gametes is capable of
providing transmission of an active state. In the case
of a small affinity, an active state cannot be trans
mitted through male gametes. Therefore, inheritance
of epigene states in some individuals may occur only
through maternal lines.
Epigenes may accidentally change their func
tional state and structure. Thus, new functional state
can be absorbed during crosses between individuals
containing epigenes in different states. Structural
changes (mutations) may affect the structural gene
included in the scripton, receptor zone and the
regulatory gene. Mutations of the structural gene
result either in inactivation of the product of this gene
(a phenotypically mutant gene does not manifest
itself) or in the change of some characteristics of the
product without its inactivation (a phenotypically
mutant gene manifests itself). In the case of inac
tivation of the product, the active and inactive states
of the mutant gene are phenotypically indistinguis
hable; but the results of some crosses will depend on
the state of this gene. For example, we may obtain
the following two crosses:
A IA x a Ia —>A Ia ; A IA x a Ia —-*A la ,
where A, is a nonmutant gene and a is a mutant gene.
As a result of the absorption, the gene A manifests
itself in the former hybrid, whereas in the latter — it
does not.
We are now concerned with the case when the
structural gene mutation results only in the change of
some characteristics of the product, and the mutant
gene in an active state manifests itself in individuals
containing in a homologous chromosome a normal
allele of this gene in an active state. For two alleles
A{ (normal) and A2 (mutant) of the structural gene,
six epigenotypes:
Ax IA\ , A\ IAx , Ax IA2 , A{ IA2 , A2 IA2 , A2 IA2 ,
and 4 phenotypical classes are possible. Mutations of
the receptor zone of the scripton and the regulatory
gene may be responsible for the case where the
activator of each epigene is specific only to the
receptor zone of its epigene, the diversity of the
possible epigenotypes increases and assumes the fol
lowing form:
A\ IA\ , A\ IA\ , A\ IA2 , A\ IA2 , A\ IA2 , Ax IAD2 ,
A2 IA2 , A2 IA2 .
77
RUSTEM N. TCHURAEV
Fig. 3. Two-operon trigger:
the operon D transcription;
the operon С transcription
d — repressor of
с — repressor of
Two-Operon Trigger. We proceed next to the
simplest cyclic system possessing the properties of the
epigene (Fig. 3). This system is a two-component
trigger suggested for the first time by Monod and
Jacob [8 ]. Later on, the models of such systems were
investigated by different methods [9, 10].
It was shown that they have two alternative
states. In the system, described in Fig. 3, both
components contain a regulatory gene, the protein
product of which represses the activity of the other
component.
We are now examining an epigene presented by
such a cyclic two-component system. Let both genes
of the system be located on a chromosome, and the
repressors of the trigger are stable proteins. Crosses
between individuals of the same epigenotype will yield
offspring with the parental epigenotype. For example,
CLD°/CLD° x C]D°/CLD° C]D°/CLD°.
In crosses between individuals which different
epigenotypes, CLD°/C]D° x (fDL/C0D{ the epigenes
will behave in a complex fashion. In this case, the
repressors pass from the gametes to the zygotes for
each gene of the trigger, and both will be turned off
for sometime. Sequential cell divisions will dilute the
repressors.
Eventually, some cells will accidentally contain
repressors of one kind and the others will possess
repressors of the other kind. Accordingly, the epi
genotypes of some cells will be C0DL /C0D\ and those
of the remaining cells will be CLD°/CLD°. The ratio of
cells with different epigenotypes will depend on the
relative concentration of the two kinds of repressors
in zygote.
To illustrate the appearance of cells with different
epigenotypes during a namber of cell division, we may
take the simplest case. Let the repressor concentration
in the zygote make up 4 molecules per cell for the
gene D and 2 molecules per cell for the gene C. The
dilution of the repressors during subsequent sequen
tial cell division is shown in Fig. 4. Each division will
decrease the concentration of repressors per cell, on
the average, by half until there emerge cells con
taining one molecule of each repressor. It is easily
understood that shortly afterwards or with the comp
letion of a certain number of divisions, cells with
different epigenotypes
C°DL/C°DL or CLD°/CLD°
may be expected to form. The trigger system ensures
constancy of each of these states during sequential
cell division.
The kind of gamete epigenotypes of such orga
nism depends on whether the reproductive pathway
has been established prior to or after stabilization of
the states
C°DX/C*D\CXD°/C{D\
Individuals with an early pathway establishment
(individuals of the type I) will produce gametes of two
kinds: C°DL and CLD°. Individuals with a late (in the
aforementioned sense) pathway establishment (indi
viduals of the type II) will give rise either to gametes
with C°DL or to gametes with CLD° epigenotypes only.
In this case, the kind of gametes of the concrete
individual is accidental.
Thus, depending on the peculiarities of the
ontogenesis of partners, crosses between individuals
with different epigenotypes CLD°/CLD° x C°DL/C°DL
may yield offsprings producing gametes of two kinds
or offsprings producing gametes of one kind only.
CD/CD will be taken to designate epigenotypes of the
offsprings producing gametes of two kinds and
C25/CS-epigenotypes of the offsprings producing ga
metes of only one kind. For simplicity, we shall
restrict ourselves to the operon С of the trigger
system. The active state of the operon С is assumed
to manifest itself phenotypically in the presence of a
certain biochemical product. Hence, this product^ may
be present in individuals with epigenotypes C/C and
C/C which phenotypically will prove similar to indi
viduals with epigenotype CVC 1 . Using the accepted
designations, the outcome of crosses between indivi
duals of the type I may be described as:
1. CVC 1 x c7c° c/C — formation of a «hybrid»;
;2. C/C x c V C 1 - C/C; C 7 C
3. C/C x c°/C° -*C/C; C°/C° — analogue of the
analysed cross;
4. C/C x c/C -* CVC 1 ; C7C° ; C/C — splitting.
78
THE EPIGENE HYPOTHESIS
Fig. 4. Dilution of trigger repressors during zygote divisions (for
explanations see text)
Thus, in this case, offsprings of three kinds with
the same genotypes is possible. Such a behaviour of
individuals C / C during crosses let them to be referred
to as epiheterozygotes. It may be easily seen that in
the described situation the epigene «mimies» is a true
gene. Actually, analogous phenotypes occur as a
result of the crosses of the kind 1—4, provided that
instead of a pair of epigenes differing only in states,
we take a pair of alleles С and с differing structurally.
It is obvious that individuals with epigenotypes
C/C cannot be regarded as epiheterozygotes, because
each of them produces gametes of only one kind.
When individuals are crossed with epigenes con
taining different structural genes but having the same
receptor zones,
CxDx/C2D2*CxDxlC2D2,
as a result of the combination of chromosomes and
crossing-over, will yield 9 genotypical and 18 epi-
genotypical classes:
If C 2 and C Y , D2 and Dx are codominant, these
epigenotypes correspond to six phenotypes. The cros
sing-over between С and D does not manifest itself
phenotypically, because in each trigger one gene is
turned off.
To conclude, we shall sum up the results of the
analysis of crosses between individuals differing in
epigenotypes only. The following events may be
expected to occur in offspring from crosses between
individuals containing epigenes in different states.
The manner in which these events are manifest
depends on the underlying epigene mechanisms and
on the features of ontogenesis:
1. Absorption (offspring will have epigenes in the
same states).
2. Formation of an epiheterozygote organism
producing gametes of different kinds.
3. Formation of offsprings with each producing a
gamete of one kind and individuals differing in the
kind of the gametes produced.
Diagnostic Experiments and Some Facts. Let us
describe the means which may be experimentally
helpful in identification of the existence of epigenes.
In the case of their existence, the functional state of
some genes subordinated to epigenes can be changed,
and this change will be inherited by subsequent
generations though the structure of genes in itself has
not changed. The phenomenon of absorption consis
ting in unification of states of genes subordinated to
epigenes, observed as early as in the first generation,
with a consequent absence of splitting may serve as a
diagnostical feature of epigene existence. The ^situa
tion is more complex when epigenotypes A/A and
Я/Я are formed. In cases like this the existence of
epigenes may be identified in the following way. We
assume the existence of some gene A subordinated to
the epigene. The chromosome, wherein the gene A is
located, has the marker M of the dominant gene
coupled to the gene A. The idea of the experiment is
to change the state of the gene A through crossing
and watch the behaviour of the marked chromosome.
We assume the crosses: AlM/A]M x A°/A°. Accor
dingly, depending on the type of partners, we shall
have in the first generation either individuals AMI A
or ЯМ/Л. ^Let us examine the first case: AlM/A]M *
x A°/A°^> AMIA. The epiheterozygote will produce
gametes of the following kinds: A°M, AlM, A] and A0
including gametes, containing the marker and the
gene A in the state alternative to the initial one. Such
gametes will occur in crosses:
AMI A x A0/A0 - A°M/A°; A0/A0; AM/A; A/A
with the resulting individuals A°M/A° having the
marker and the gene A in an inactive state. Pheno
typically, this will manifest as the absence of the
effect of the gene A.
The analogous^ crosses between individuals with
epigenotypes AMI A and A0/A0 will also yield indi
viduals A0 Ml A0. The formation of such individuals
79
RUSTEM N. TCHURAEV
serves to indicate the existence of epigenes, because
the change of state of the marked chromosome is the
only way of their formation.
In the case of the absence of epigenes, the result
of the experiments with individuals containing the
marked chromosome will be as follows: AMIAM x
x а/a -* AMIa. Phenotypically, the individual AM I a
may look as individuals with epigenotypes AMI A and
ЯМ/Л. However, after the second cross: AM I a x
x а/a AMI a; a/a the two types of individuals are
formed. Individuals of the first type are characterized
by the presence of the marker M and the effect of the
gene Л, whereas those of the second type — by their
absence.
The inheritance of nonmutational changes, indu
ced by external agents, may also testify to the
existence of epigenes. An illustrative case is the data
obtained in studies of the effect of heat shock on the
development of macrochaetae in the forked mutants of
Drosophila melanogaster [11, 12].
Four critical periods have been established during
development of macrochaetae. The first period inclu
des the early stages of ontogenesis (some 6—7 days
before laying of eggs); the second includes the stage
when eggs have been just laid; the third period is
observed at the 14th hour of embryogenesis and the
fourth refers to the prepupal stage of development
(5th day of a larval life). Exposure to heat (or cold)
during these periods, depending on the duration of
thermal treatment, induces either a decrease (short-
term thermal treatment) or an increase (long-term
treatment) in the number of abnormal macrochaetae.
These changes are transmitted to a large number of
successive generations. For example, warming of flies
to 38 °С for 30 minutes at the first critical period
decreases the number of abnormal macrochaetae, and
this decrease is a maternally inherited character
retained by twenty to thirty (sometimes, even more)
subsequent generations [12, 13]. Based on some
definite arguments, Svetlov and Korsakova conclude
that these changes are not mutations. The main
argument used was the fact that the number of
abnormal macrochaetae is reduced inall offspring
from thermally treated parents.
The phenomenon of «absorption» is another diag
nostic feature of epigene existence. Phenotypically,
«absorption» resembles paramutations, which are the
consequence of the heterozygous association of a
paramutable allele with a paramutagenic allele; the
resulting paramutable alleles are inherited by sub
sequent generations. Examples of paramutations are
those occurring at locus R in maize [13]. The three
alleles at locus R are R\ r* and Rst.
Rr controls the formation of anthocyan in plants
and in aleurone endosperm. The endosperm is tri-
ploid, because its cells receive a double set of genes
from the maternal plant and a single set from the
paternal one. The allele Rr in a single dose (R'Yr*)
gives rise to a dark-dotted aleurone a dark one-colour
aleurone in a double or triple dose. The recessive
allele is responsible for the absence of anthocyan in
plants as well as in the aleurone. The alleles Rst gives
a spotted pattern of the aleurone, the number of spots
being proportional to the dosage of this allele. The
existence of paramutations is illustrated by the follo
wing experiments. Three crosses are conducted:
1) Л* О X RrRr;
2) ,V О X RstR5t;
3) / V О X RrR5t.
The following endosperm genotypes are expected
to occur:
1) all with Rr r* r* genotype.
2) all with Rst r* r* genotype.
3) 50 % with Rr T* r* and 50 % with R5t r* r8
genotypes.
Spotted seeds with genotypes R5t r* r*, expected
from crosses 2 and 3, do not differ phenotypically; all
seeds with Rr r* r* constitution, derived from crosses
1 and 3, differ. All seeds with Rr r* r* genotype
derived from cross 3, contain, on the average, half the
pigment contained in seeds from cross 1. The allele
R\ after heterozygous association with allele R5t,
passes into another state, designated as Rrl. This
change is inherited and manifests in decreased capa
city for anthocyan formation. The Rr-+ R'l transition
is a paramutational change. The phenomenological
similarity between paramutation and absorption lies
in the inheritance of one of its alleles after their
heterozygous association with another allele. Para
mutation leads to a functional change of the allele Rr,
not a structural one, perhaps, because this allele falls
into state Rr\ in almost all the Rr gametes in plants
with Rr R5t constitution.
From an evolutionary point of view, the existence
of epigenes, «the so to say second supplementary flux
of hereditary information*, might apparently give
some advantages to their possessors. When epigenes
are in inactive state, mutations of subordinated genes
are not manifested and look quite neutral. Thus,
accumulation of mutations, their realization and esti
mation through natural selection by switching on the
respective epigenes is possible. Besides, the organism
possessing epigenes would enable to approve different
hereditary changes without changes of the genome,
and this may serve as a material for natural selection.
To sum it up, we may conclude that epigenes are
really existing in nature at least in A-phage and other
lambdoid phages. As for eukaryotes, though the
80
THE EPIGENE HYPOTHESIS
existence of such systems is not shown experi
mentally, some facts may be successfully viewed from
the standpoint of the epigene hypothesis. This hypo
thesis may prove to be useful to explain a number of
data which cannot be explained within the frames of
conventional Mendelian notions.
I am thankful to D. K. Belyaev, M. D. Go-
lubovski, E. V. Gruntenko, L. L Korochkin, V. A.
Kulichkov, Z. S. Nikoro, V. A. Ratner and V. V.
Khvostova for their constructive discussion and valu
able criticism, of the paper and I acknowledge the
technical aid rendered by G. Kh. Ziganshina and
I. G. Migranova.
Гіпотеза про епіген
P. H. Чураєв
Резюме
Запропоновано гіпотезу про епіген — одиницю, у якій: а) спад
кова інформація кодується не лише послідовностями основ у
молекулах ДНК, але й іншим способом, наприклад, при
сутністю або відсутністю визначених регуляторних білків; б)
зберігання спадкової інформації протягом життя клітини
забезпечується наявністю зворотних зв'язків; в) передача
спадкової інформації від батьківської особини до нащадків
здійснюється шляхом розподілу позагеномних макромолекул
регулюючих речовин. Розглянуто моделі найпростіших систем
з ознаками епігена. При схрещуванні особин, що містять
епіген у різних станах в залежності від конкретного виду
епігена та особливостей онтогенезу, у потомстві від схрещу
вань можуть статися наступні події: поглинання (нащадки
матимуть епігени в однакових станах); 2) виникнення епіге-
терозиготи, яка дає гамлети різних сортів; 3) формування
таких особин, кожна з яких виробляє лише один сорт гамет,
але різні особини здатні виробляти різні сорти гамет. Запро
поновано ідею експеримента, що дозволяє виявити епігени
шляхом схрещування.
Гипотеза об эпигене
P. Н. Чураєв
Резюме
Предложена гипотеза об эпигене — единице, в которой: а)
наследственная информация кодируется не только последова
тельностью оснований в молекулах ДНК, но и другим спосо
бом, например, присутствием или отсутствием определен
ных регуляторних белков; б) хранение наследственной инфор
мации в течение жизни клетки обеспечивается наличием
обратных связей; в) передача наследуемой информации от
родительской особи к потомству происходит путем распреде
ления вне геномных макромолекул регулирующих веществ. Рас
смотрены модели простейших систем, обладающих свойства
ми эпигена. При скрещивании особей, содержащих эпигены в
разных состояниях в зависимости от конкретного вида эпи
гена и особенностей онтогенеза, в потомстве от скрещиваний
могут произойти следующие события): 1) поглощение (по
томство будет иметь эпигены в одинаковых состояниях; 2)
образование эпигетерозиготы, дающей гамлеты разных сор
тов; 3) образование таких особей, каждая из которых произ
водит лишь один сорт гамет, но разные особи могут произво
дить разные сорта гамет. Предложена идея эксперимента,
позволяющего выявить эпигены путем скрещиваний.
REFERENCE
1. Ratner V. A., Tchuraev R. N. Does a two-operon control
system (trigger) exist? Some facts and the heuristic importance
of the trigger / / Genet ika.—1971.—7, N 9 .—P. 175—179.
2. Oppenheim А. В., Neubauer Z., Calef E. The antirepressor
new element of the regulation of protein synthesis / / Nature.—
1970.—226, N 5 2 4 0 . — P . 31 .
3. Nijkamp H. J. J., Szybalski W., Calef E. Antirepressor controls
tetranscription of the repressor operon of lambda phage / /
Informative Molecules in Biology Systems.—Amsterdam: North-
Holland Publ. Co., 1971 .—P. 241 .
4. Tchuraev R. N., Ratner V. A. About operon system modelling
in the language of automata theory / / Genetika. —1971 . — 9 ,
N 2 .—P. 173.
5. Echols H., Green L. Establishment and maintence of repression
by bacteriophage lambda: the role of the Cb Cn and C n i
proteins / / Proc. Nat. Acad. Sci. U S A . — 1 9 7 1 . — 6 8 , N 9.—
P. 2190.
6. Davidson E. Gene activity in early development.—Moscow:
Mir, 1972.
7. Riggs A. D., Bourgeois S., Cohn M. The lac-repressor-
operator interaction. III. Kinetic studies / / J. Мої. Biol.—
1970 .—53, N 3 .—P. 401 .
8. Monod J., Jacob F. General conclusions: teleonomic me
chanisms in the processes of cell metabolism, growth and
differentiation / / Regulatory Mechanism of the Cell.—M.: Mir,
1964.—P. 477.
9. Romanovski Ju. M., Stepanova N. V., Chernavski D. S.
Mathematical modelling in biophysics.—M.: Fismatgiz, 1975.
10. Tchuraev R. N., Ratner V. A. Modelling of molecular and
genetic control systems in the language of automata theory / /
Studies on Theoretical Genetics.—Novosibirsk: Inst. Cytol.
Genet. Press, 1972 .—210 p.
11. Svetlov P. G., Korsakova G. F. Effect of the short-term heating
of the forked female mutants of Drosophila melanogaster on
the expressivity of characters of the mutation in a number of
subsequent generations / / Dokl. Acad. Nauk SSSR.—1966 .—
168, N 1.—P. 191.
12. Svetlov P. G., Korsakova G. F. Long-term modification in the
experiments with thermally treated larvae of the forked mutants
of Drosophila melanogaster II Ibid.—170, N 2 . — P . 439.
13. Brink R. A., Styles E. D., AxtellJ. D. Paramutation: directed
genetic change / / Sc ience .—1968 .—159, N 3811 .—P. 161.
УДК 575.17
Received 26.02.96
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