ISSN 1022-7954, Russian Journal of Genetics, 2009, Vol. 45, No. 3, pp. 276–286. © Pleiades Publishing, Inc., 2009.
Original Russian Text © B.F. Chadov, E.V. Chadova, E.A. Khotskina, N.B. Federova, 2009, published in Genetika, 2009, Vol. 45, No. 3, pp. 318–329.
The rule in choosing a character for genetic works,
introduced by Mendel, is its stable expression (high
expressivity) and stable inheritance (complete pene-
trance). This rule followed from the fundamental idea
that a factor (gene) is an elementary unit of inheritance,
which is not affected by variable inner and outer envi-
ronmental factors. It seemed then that the rule pre-
scribed by Mendel provided the choice of true (geneti-
cally determined) characters and excluded transient
(non-genetic) characters determined by the action of
The Mendelian approach to the choice of characters
did not alter with the beginning of the mutation era in
genetics. Artiﬁcially induced mutations also were to
display high expressivity and complete penetrance. Ide-
ally, a genetic mutation in a homozygote should be
expressed in any individual of a given species in an
unlimited number of generations.
A fundamentally new approach to choose mutations
was proposed in 2000: a mutation should be expressed
in individuals of one genotype and not expressed in
individuals of another genotype [1, 2]. It was supposed
that through selection of such mutations it is possible to
identify genes responsible for the formation of charac-
ters of intraspeciﬁc similarity [3, 4]. Characters of this
category were not studied by classical genetics .
Three techniques were developed to produce lethal
. These muta-
tions were deﬁned as conditional dominant lethals. In
individuals of one genotype such mutations manifested
themselves as dominant lethals, and in individuals of
some other genotype they were not lethal [1, 6, 7].
In addition to conditional lethality, these mutations
showed other features. They stopped being lethal in the
presence of chromosome rearrangements [3, 7] and
demonstrated the parental effect in their expression
9]. Offsprings of mutants often had complex devel-
opmental defects (morphoses) [8, 10, 11]. The capacity
to form morphoses and the conditional expression of
mutations made it possible to consider that the identi-
ﬁed genes belong to the group of regulatory genes con-
trolling ontogenesis [4, 11–13].
One more remarkable feature was demonstrated in
the course of maintenance of
cultures: the mutants appeared to be genetically unsta-
ble. The ﬁrst discovered form of instability was the loss
of lethal expression of mutations . Then other forms
were established . This publication is devoted to the
description of various forms of instability in mutants
containing conditional dominant lethals.
MATERIALS AND METHODS
Mutations in the X chromosome and in autosome 2
were obtained in 2000–2001 [1–4] (Figs. 1, 2). They
were maintained in culture for ﬁve years. From the for-
mal genetic point of view, the mutations are conditional
dominant lethals. The indicator of the lethal action of
mutations in the X chromosome is the lack of daughters
in crosses of a mutant male with females of the
strain (Fig. 1). The indicator of the lethal action of
mutations in autosome 2 is the lack of mutant off-
springs of both sexes in similar crosses (Fig. 2).
X-chromosome mutations (22 mutations) were main-
tained by two ways: in culture with attached-X chromo-
somes and in culture with a Muller-5 inversion in the
X chromosome (Fig. 3).
Conditional Lethal Mutations Shift the Genome
from Stability to Instability
B. F. Chadov, E. V. Chadova, E. A. Khotskina, and N. B. Federova
Institute of Cytology and Genetics, Russian Academy of Sciences, Novosibirsk, 630090 Russia;
Received July 27, 2007; in ﬁnal form, April 8, 2008
—The phenomenology of genomic destabilization is described in
containing radiation-induced conditional dominant lethals in the X chromosome and in autosome 2. Destabili-
zation manifests itself as (1) the loss or decrease of lethality of previously lethal mutations; (2) the loss of
expression of visible dominant mutations in an opposite homolog; (3) chromosomal instability resulting in the
loss of the X chromosome in germline and somatic cells; (4) the occurrence of novel mutations (secondary
mutagenesis); (5) the occurrence of single and mass modiﬁcations; (6) disturbances in individual development
(formation of morphoses). The key event for the shift of the genome from the stable state into the unstable one
is the occurrence of a conditional dominant lethal mutation.