ISSN 1022-7954, Russian Journal of Genetics, 2007, Vol. 43, No. 3, pp. 275–280. © Pleiades Publishing, Inc., 2007.
Original Russian Text © N.V. Roshina, E.G. Pasyukova, 2007, published in Genetika, 2007, Vol. 43, No. 3, pp. 356–362.
Recently, signiﬁcant advances have been achieved
in identifying genes that are involved in the regulation
of longevity. One of the most interesting and important
results of these studies is the fact that the genetic bases
of longevity control are similar in most distant organ-
isms, from yeast to human. An example of such evolu-
tionary conservatism is the system of genes involved in
regulation of the insulin-dependent signaling pathway.
Mutations in genes of this system enhance longevity in
and mouse (see [1–4]
for review). Longevity control also involves genes reg-
ulating oxidative stress and heat shock resistance, DNA
repair, chromatin silencing, and some others [1–4].
However, clearly that not all genetic mechanisms
underlying longevity control are known.
It has been increasingly more evident that the ner-
vous system plays a key role in longevity control .
Overexpression of some genes exclusively in neurons,
and in some cases even exclusively in motoneurons,
enhances longevity of the whole organism .
Lifespan is a quantitative trait exhibiting high
within- and among-population variation, which is
strongly inﬂuenced by environmental conditions .
The genetic component of this variation, whose pres-
ence in wild populations is conﬁrmed by selection
experiments (see, e.g., ), is still scarcely studied, in
spite of signiﬁcant progress in understanding genetic
control of longevity in general.
The aim of our study was searching for new genes
controlling longevity and responsible for variation in
this quantitative trait in
Earlier, by means
of recombination mapping, we have found several large
chromosome regions carrying genes responsible of
lifespan differences between two lines of
[7, 9]. Veriﬁcation of localization of these genes, con-
ducted using complementation tests with deletions cov-
ering some of the previously found chromosome parts,
revealed at least 15 small regions of potential localiza-
tion of genes for longevity, whose alleles differ in two
original lines, providing variation of the trait [10, 11].
The next step in this study was complementation tests
with candidate genes localized in these regions. These
tests performed with mutations of genes
conﬁrmed their role in lifespan control [11, 12]. Gene
) codes for enzyme dopa
decarboxylase, which is a key enzyme in catechola-
mine biosynthesis, essential for transforming dopa into
dopamine and 5-hydroxytriptophane into serotonine;
both substances are involved in transmission of nerve
) encodes a transcription
factor involved in motoneuron development control.
Thus, the both genes are related to the development and
functioning of the nervous system.
For further study, we also selected candidate genes
related to the development and functioning of the ner-
vous system. In the present work, we present the results
of complementation tests with the following genes:
) participates in catecholamine
) is the
regulator of tyrosine hydroxylase, the key enzyme of
dopa biosynthesis; genes
alpha metil dopa-resis-
Diphenol oxidase A2
) are involved in
metabolism of catecholamines, which are essential for
hardening and coloring of the cuticle; gene
Genes Regulating the Development and Functioning
of the Nervous System Determine Life Span
N. V. Roshina and E. G. Pasyukova
Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, 123182 Russia;
fax: (495) 196-19-09; e-mail: firstname.lastname@example.org
Received July 27, 2006
—Earlier, it has been shown that genes responsible for differences in longevity between wild-type
lines 2b and Oregon are localized in region 7A6–B2, 36E4–37B9, 37B9–D2, and
64C–65C. Quantitative complementation tests were conducted between the gene mutations localized in these
regions and involved in catecholamine biosynthesis
Diphenol oxidase A2
and neuron development control
, on the one hand, and two different normal alleles of these genes in lines 2b and Oregon,
on the other. Complementation was found for genes
iav, Fas3, amd,
The remaining genes (
) are candidate genes for controlling differences in longevity between lines 2b and Oregon.