Genetic control of mitosis. Premature beginning of telophase chromatin reorganization in cells of the Drosophila melanogaster strain with ff3 mutation

The effect of cell cycle mutation ff3 on chromosome segregation was studied on fixed cells of neural ganglia. The cell distributions by diameter of interphase nuclei and by distance between sister chromatid sets were compared at anaphase and telophase. In the control wild-type strain Lausenne, the cell distribution by distance between sister chromatids in anaphase was similar to their distribution by nuclear size. The mean distance between segregating chromatids at anaphase (lcp) coincided with the mean diameter of interphase nuclei (dcp) and was 8.3 microns. Cells passed to telophase when chromatids were at least 10 microns apart. The mutant ff3 strain differed from the control strain Lausenne in cell distribution by interphase nuclear diameter and distance between sister chromatids in anaphase; the mean nuclear diameter and mean distance between segregating chromatids similarly increased to 9.3 microns. A specific feature of mitosis in mutant strain ff3 was a premature beginning of telophase chromatin reorganization. This caused the occurrence of cells with abnormally short (less then the interphase nuclear diameter) distance between sister chromatid sets in telophase but not in anaphase, as if these cells had passed from anaphase to telophase prematurely, during the chromatid movement toward poles in anaphase A.     

Genetic Control of Mitosis: Features of Anaphase Separation of Sister Chromatid Sets in Mutant Strain aar V158 in Drosophila melanogaster

The effect of mutation aar ^V158 on anaphase separation of chromatids was studied on fixed cells of neural ganglia of Drosophila melanogaster larvae. It was shown that mutation aar ^V158 causes three types of defective chromosome segregation manifested as (1) monopolar anaphase, (2) separation of chromatids to an abnormally short distance in anaphase, and (3) bridging and lagging of some chromatids or prolonged asynchronous separation of sister chromatid sets to the poles in anaphase. We believe that the former two types of defective segregation are caused by disturbed centrosome separation at the beginning of mitosis and the third type, by defects in chromatid separation during anaphase. During the two-year maintenance of the mutation in a heterozygous state, partial correction (adaptive modification) of the defects of type 1 and type 2 (but not type 3) occurred. The correction of type 1 and type 2 defects during adaptogenesis depended on the genotype: in heterozygotes and homozygotes, respectively type 1 and type 2 were preferentially corrected. The frequency of type 3 defects remained constant during the two-year period of maintenance of the mutation in a heterozygous state. However, in all variants of the experiment, their frequency decreased with increasing distance between the sister chromatid sets. In the cells that completed the previous division with abnormalities, the checkpoint system is supposed to effectively arrest the cell cycle in the subsequent division.     

Genetic Control of the Formation and Reorganization of Chromocenter in Drosophila

The chromocenter integrates the entire Drosophilagenome into a unit. The formation and reorganization of chromocenter are genetically determined. Currently, several mutations affecting the structure of chromocenter have been described. In this work, I present evidence on the time of the formation and reorganization of chromocenter in mitotic and meiotic cells of females of the wild type and the ff16mutant line obtained by selection of mosaic clones produced from mitotic recombination of chromosomes in the dividing embryo cells. In females homozygous for this mutation, the second stage of the formation of chromocenter (joining two groups of nonhomologous chromosomes X-4 and 2-3 into a united ring structure =X=2=3=4=) is disturbed. The differences between the mitotic and meiotic reorganization of chromocenter and the role of chromocenter in the control of chromosome segregation are discussed.     

Genetic Control of Development of Malpighian Tubules in Drosophila melanogaster

Malpighian tubules of insects are a functional analog of mammalian kidneys and serve as a classical model for studying the structure and functions of transport epithelium. The review contains the data on structural organization, functioning, and formation of the Malpighian tubules during embryogenesis in Drosophila melanogaster. Various systems of genes are described that control the program of development of the renal (Malpighian) tubules in D. melanogaster. A special attention is paid to the ways of signal transduction and factors involved in cell differentiation, proliferation, and morphological transformation during development of the Malpighian tubules. Evolutionarily conservative genetic systems are considered that are involved in the control of development of both the renal epithelium ofDrosophila and mammalian kidneys. A relationship was noted between the disturbed balance of genetic material and congenital defects of the human excretory system.     

Genetic Basis of Sexual Isolation in Drosophila melanogaster

Sexual isolation between Zimbabwe (abbreviated as Z) and cosmopolitan (abbreviated as M) races exists in Drosophila melanogaster. Typically, when given a choice, the females from the Zimbabwe race mate only with males from the same race, whereas females from the cosmopolitan race mate readily with males from both races non-discriminatorily. Genetic tools available in this experimental organism permit the detail genetic analyses of the sexual isolation behavior. On the other hand, the search for the actual signaling systems involved in the mate recognition is still limited in this system. In this paper, we review the studies, which attempt to dissect the genetic basis of the sexual isolation system, and document the complex features of the genetic architecture and the behavioral traits that evolved at an incipient stage of speciation. The evolution and the maintenance of this behavioral polymorphism are also discussed.     

Genetic control of macrochaetae development in Drosophila melanogaster

The Drosophila head and body have a regular species-specific pattern of strictly defined number of external sensory organs--macrochaetae (large bristles). The pattern constancy and relatively simple organization of each bristle organ composed of only four specialized cells makes macrochaetae a convenient model to study the developmental patterns of spatial structures with a fixed number of elements in specific positions as well as the mechanisms of cell differentiation. The experimental data on the major genes and their products controlling three stages of macrochaetae development--the emergence of proneural clusters in the imaginal disc ectoderm, the precursor cell determination in the proneural clusters, and the specialization of cells of the definitive sensory organ--were reviewed. The role of the achaeta-scute gene complex, EGFR and Notch signaling, and selector genes in these processes was considered. Analysis of published data allowed us to propose an integrated diagram of the system controlling macrochaetae development in D. melanogaster.     

Genetic analysis of muscle development in Drosophila melanogaster

The different thoracic muscles of Drosophila are affected specifically in the mutants: stripe (sr), erect wing (ewg), vertical wings (vtw), and nonjumper (nj). We have tested the extent of this specificity by means of a genetic analysis of these loci, multiple mutant combinations, and gene dosage experiments. A quantitative, rather than a qualitative, specificity is found in the mutant phenotypes. All muscles are altered by mutations in any given gene, but the severity of these alterations is muscle specific. The locus stripe seems to have a polar organization where different allelic combinations show quantitative specificity in the muscle affected. In addition to the muscle phenotypes, neural alterations are detected in these mutants. The synergism found between ewg, vtw and ewg, sr as well as the dosage effect of the distal end of the X chromosome upon the expression of ewg and sr suggests the existence of functional relationships among the loci analyzed.     

Chromatin structure of a P-element-transduced hsp-28 gene in Drosophila melanogaster.

The Drosophila hsp-28 gene was heat inducible when transduced to novel chromosomal sites even when no direct selection for transduced gene expression was imposed. The pattern of DNase I-hypersensitive sites 5' to the wild type and transduced copy of hsp-28 was similar. In addition, DNase I-hypersensitive sites occurred within the P-element sequences flanking transduced loci.     

Mutation Indy p115 Extends Life Span in Adult Drosophila melanogaster Depending on Sex and Genetic Background

The Indy ^p115 allele in heterozygous state almost doubles the life span of adult Drosophila melanogaster, and this effect largely depends on the strain used for obtaining heterozygotes. Male and female life span depends on Indy ^p115 to a different degree. Apart from Indy ^p115 heterozygotes, sexual dimorphism for life span was also observed in strain Hikone-AW, but not in Oregon R and TM3 balancer. In heterozygotes Indy ^p115/OR, both the average life span and female reproductive period increased as compared to OR control. No substantial increase in female reproductive period in Indy ^p115/Hk heterozygotes was found. In homozygotes for allele Indy ^p115, we have previously revealed two phases of embryotic lethality and lethality at the larval and pupa stages. Thus, allele Indy ^p115 has a double and opposite effect on Drosophilaviability. On the one hand, it extends the life span of adult flies, on the other, decreases survival at preimaginal stages.     

Genetic variation affecting heart rate in Drosophila melanogaster

Heart rate in pre-pupae of Drosophila melanogaster is shown to vary over a wide range from 2.5 to 3.7 beats per second. Quantitative genetic analysis of a sample of 11 highly inbred lines indicates that approaching one-quarter of the total variance in natural populations can be attributed to genetic differences between flies. A hypomorphic allele of the potassium channel gene ether-a-gogo, which is homologous to a human long-QT syndrome susceptibility gene (HERG), has a heart rate at the low end of the wild-type range, but this effect can be suppressed in certain wild-type genetic backgrounds. This study provides a baseline for investigation of pharmacological and other physiological influences on heart rate in the model organism, and implies that quantitative genetic dissection will provide insight into the molecular basis for variation in normal and arrhythmic heart function.     

Polygenic Mutation in Drosophila Melanogaster: Genetic Analysis of Selection Lines

We have conducted genetic analyses of 12 long-term selection lines of Drosophila melanogaster derived from a highly inbred base population, containing new mutations affecting abdominal and sternopleural bristle number. Biometric analysis of the number of effective factors differentiating the selected lines from the base inbred indicated that with the exception of the three lines selected for increased number of abdominal bristles, three or more mutations contributed to the responses of the selection lines. Analysis of the chromosomal distribution of effects revealed that mutations affecting abdominal bristle number occurred on all three major chromosomes. In addition, Y-linked mutations with effects ranging from one to three bristles occurred in all three lines selected for decreased number of abdominal bristles, as well as in one line selected for increased abdominal bristle number. Mutations affecting sternopleural bristle number were mainly on the X and third chromosomes. One abdominal and one sternopleural selection line showed evidence of a segregating lethal with large effects on bristle number. As an indirect test for allelism of mutations occurring in different selection lines, the three lines selected in the same direction for the same trait were crossed in all possible combinations, and selection continued from the F(2) hybrids. Responses of the hybrid lines usually did not exceed those of the most extreme parental lines, indicating that the responses of the parental lines may have been partly due to mutations at the same loci, although other interpretations are possible.     

Control of oxidative stress resistance by IP3 kinase in Drosophila melanogaster

Oxidative damage is thought to be a major causal factor of aging, and is implicated in several human pathologies such as Alzheimer's and Parkinson's diseases. Nevertheless the genetical determinants of in vivo oxidative stress response are still poorly understood. To identify cellular components whose deregulation leads to oxidative stress resistance, we performed a genetic screen in Drosophila melanogaster. We thus identified in this screen Drosophila Inositol 1,4,5-triphosphate kinase I (D-IP3K1), a Drosophila gene homologous to mammalian IP3Ks. In vertebrates, IP3Ks phosphorylate the second messenger Inositol 1,4,5-triphosphate (IP3) to produce Inositol 1,3,4,5 tetrakiphosphate (IP4). IP3 binding to its receptor (IP3R) triggers Ca(2+) release from the endoplasmic reticulum (ER) to the cytosol, whereas IP4 physiological role remains elusive. We show here that ubiquitous overexpression of D-IP3K1 confers resistance of flies to H(2)O(2)- but not to paraquat-induced oxidative stress. Additional genetic analysis with other members of IP3 and IP4 signaling pathways led us to propose that the D-IP3K1 protective effect is mainly mediated through the reduction of IP3 level (which probably results in reduced Ca(2+) release from internal stores), rather than through the rise of IP4 level.     

A Comprehensive Study of Genic Variation in Natural Populations of Drosophila melanogaster. III. Variations in Genetic Structure and Their Causes between Drosophila melanogaster and Its Sibling Species Drosophila simulans

The natural populations of Drosophila melanogaster and Drosophila simulans were compared for their genetic structure. A total of 114 gene-protein loci were studied in four mainland (from Europe and Africa) and an island (Seychelle) populations of D. simulans and the results were compared with those obtained on the same set of homologous loci in fifteen worldwide populations of D. melanogaster. The main results are as follows: (1) D. melanogaster shows a significantly higher proportion of loci polymorphic than D. simulans (52% vs. 39%, P<0.05), (2) both species have similar mean heterozygosity and mean number of alleles per locus, (3) the two species share some highly polymorphic loci but they do not share loci that show high geographic differentiation, and (4) D. simulans shows significantly less geographic differentiation than D. melanogaster. The differences in genetic differentiation between the two species are limited to loci located on the X and second chromosomes only; loci on the third chromosome show similar level of geographic differentiation in both species. These two species have previously been shown to differ in their pattern of variation for chromosomal polymorphisms, quantitative and physiological characters, two-dimensional electrophoretic (2DE) proteins, middle repetitive DNA and mitochondrial DNA. Variation in niche-widths and/or genetic strategies of adaptation appear to be the main causes of differences in the genetic structure of these two species.     

Molecular Genetic Analysis of Ethanol Intoxication in Drosophila melanogaster

Recently, the fruit fly Drosophila melanogaster has been introducedas a model system to study the molecular bases of a varietyof ethanol-induced behaviors. It became immediately apparentthat the behavioral changes elicited by acute ethanol exposureare remarkably similar in flies and mammals. Flies show signsof acute intoxication, which range from locomotor stimulationat low doses to complete sedation at higher doses and they developtolerance upon intermittent ethanol exposure. Genetic screensfor mutants with altered responsiveness to ethanol have beencarried out and a few of the disrupted genes have been identified.This analysis, while still in its early stages, has alreadyrevealed some surprising molecular parallels with mammals. Theavailability of powerful tools for genetic manipulation in Drosophila,together with the high degree of conservation at the genomiclevel, make Drosophila a promising model organism to study themechanism by which ethanol regulates behavior and the mechanismsunderlying the organism's adaptation to long-term ethanol exposure.     

Genetic control of programmed cell death in Drosophila melanogaster

Apoptosis is a genetically controlled form of cell death that is an important feature of animal development and homeostasis. The genes involved in the control and execution of apoptosis are conserved throughout evolution. However, the actual molecular mechanisms used by these genes vary from species to species. In this review, we focus on the genetic components of apoptosis in the fruit fly Drosophila melanogaster, and compare their mode of action to the one employed by the homologous genes in mammals. We also cover recent advances that show that apoptotic genes have a requirement in processes other than apoptosis.     

Genetic analysis of mitochondrial protein misfolding in Drosophila melanogaster

Protein misfolding has a key role in several neurological disorders including Parkinson's disease. Although a clear mechanism for such proteinopathic diseases is well established when aggregated proteins accumulate in the cytosol, cell nucleus, endoplasmic reticulum and extracellular space, little is known about the role of protein aggregation in the mitochondria. Here we show that mutations in both human and fly PINK1 result in higher levels of misfolded components of respiratory complexes and increase in markers of the mitochondrial unfolded protein response. Through the development of a genetic model of mitochondrial protein misfolding employing Drosophila melanogaster, we show that the in vivo accumulation of an unfolded protein in mitochondria results in the activation of AMP-activated protein kinase-dependent autophagy and phenocopies of pink1 and parkin mutants. Parkin expression acts to clear mitochondria with enhanced levels of misfolded proteins by promoting their autophagic degradation in vivo, and refractory to Sigma P (ref(2)P), the Drosophila orthologue of mammalian p62, is a critical downstream effector of this quality control pathway. We show that in flies, a pathway involving pink1, parkin and ref(2)P has a role in the maintenance of a viable pool of cellular mitochondria by promoting organellar quality control.