1022-7954/01/3706- $25.00 © 2001 MAIK “Nauka /Interperiodica” 0593 Russian Journal of Genetics, Vol. 37, No. 6, 2001, pp. 593–602. Translated from Genetika, Vol. 37, No. 6, 2001, pp. 725–736. Original Russian Text Copyright © 2001 by Tretyakova, Lyozin, Markova, Evgen’ev, Mamon. INTRODUCTION Genes controlling the key processes in cell metabo- lism are generally evolutionarily conserved and have orthologs in various organisms including those belong- ing to remote taxa. Mutations of such genes often are pleiotropic. One of these genes in Drosophila melano- gaster is sbr (small bristles) whose mutant alleles affect essential organism and cell processes including cell response to stress, meiotic chromosome segregation, embryonic development, and mutagenesis [1]. Com- paring these genes and their products in various organ- isms has become a promising area of research in a new field of genetics termed genomics. To examine func- tions of orthologous genes in detail, well-elaborated models are helpful. Drosophila melanogaster is a unique model for molecular genetic studies of chromo- some disjunction in cell division. For this organism, an extensive collection of mutants with defective meiotic and mitotic chromosome segregation exists and genetic methods of estimating nondisjunction frequencies and loss of all genome chromosomes in meiosis have been developed. MUTATION l(1)ts403 IN D. MELANOGASTER l(1)ts403 is an allele of the sbr locus in D. melano- gaster. The l(1)ts403 mutation was isolated by R. Ark- ing and described as a cell ts lethal with restrictive tem- perature of 29°C [2]. One of the first revealed manifes- tations of this mutation was the disruption of synthesis of heat shock proteins (HSPs) at the posttranscriptional level [3–5]. As Hsp genes occur in all organisms from bacteria to human and are evolutionarily conserved, we should expect that a gene whose mutation affects their expression is also evolutionarily conserved and organ- isms other than Drosophila have its orthologs. Moreover, heat treatment induces a wide variety of pleiotropic effects of the l(1)ts403 mutation, the most interesting of which, as we think, is meiotic sex-chro- mosome nondisjunction in D. melanogaster females subjected to heat shock (HS) [6, 7]. This manifestation is semidominant in contrast to the impairment of HSP synthesis, which is recessive [1]. In the l(1)ts403 strain, heat shock also disrupts mitotic cell proliferation [8], condensation of mitotic chromosomes [9], embryonic development [1] and morphogenesis of various struc- tures in larvae [2] and flies [10]. Collectively, these data indicate that the product of the l(1)ts403 gene is involved in the control of processes at the cellular and organism levels. The l(1)ts403 mutation as an allele of the sbr locus was genetically mapped to the 32.53–32.67-cM region of the X chromosome [11]. Cytologically it was mapped to the 9F5-6–9F8-11 region of D. melano- gaster polytene chromosomes between distal break- points of deletions Df(1)v L3 (L3, sbr not deleted) and Df(1)v L4 (L4, sbr deleted) [12]. The other name of l(1)ts403, sbr 10 (small bristles) indicates that this muta- tion belongs to the group of sbr alleles. Phenotypically, these alleles are characterized by altered bristle mor- phology (shortened thin bristles) and by the absence of some bristles (micro- and macrochaetae) on different The sbr Gene Product in Drosophila melanogaster and Its Orthologs in Yeast (Mex67p) and Human (TAP) I. V. Tretyakova 1 , G. T. Lyozin 2 , E. G. Markova 1 , M. B. Evgen’ev 2 , and L. A. Mamon 1 1 Department of Genetics and Breeding, St. Petersburg State University, St. Petersburg, 199034 Russia; fax: (812) 328-05-41; e-mail: mamon@lm2010.spb.edu 2 Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Moscow oblast, 142290 Russia; e-mail: evgenev@icb.psn.ru Received December 28, 2000 Abstract—A DNA sequence from the 9F region of Drosophila melanogaster polytene chromosomes was cloned. Sequencing the cloned region and its comparison with the known sequences of the D. melanogaster genome showed that the cloned DNA part contains gene sbr and adjacent sequences. The literature data on the structure and functions of genes TAP in humans and Mex67 in yeast are discussed. These genes are orthologous to the sbr gene of Drosophila and control mRNA export from the nucleus to the cytoplasm. The literature evi- dence is consistent with the recessive expression of mutation l(1)ts403 (sbr 10 ) upon heat treatment that is man- ifested as impaired HSP synthesis at the posttranscriptional level. However, it fails to explain the semidominant effect of the mutation manifested in high frequency of meiotic sex-chromosome nondisjunction in heat-treated females. A comparison of amino-acid sequences corresponding to the products of the three orthologous genes, TAP, Mex67, and sbr , showed that the sbr gene product of Drosophila is more similar to the human TAP factor than to the Mex67 factor in yeast. THEORETICAL PAPERS AND REVIEWS