FlyBase curator comment: in FBrf0111803, "flex" mutations are stated cause female-specific lethality due to an effect on Sxl. In FBrf0111803, "flex" mutations are stated suppress the male lethality caused by Sxl^M mutations and "flex⁺" is stated to be a positive regulator of Sxl, essential for female-specific splicing and required for the expression of Sxl protein. However, in FBrf0134557 "flex" mutations are found not to suppress even the weakest Sxl^M alleles, arguing against the relationship between "flex" and Sxl proposed in FBrf0111803. Instead, in FBrf0134557, it is shown that the lethality of "flex" mutants is due to a defect in the X-linked bb locus, since the lethality is rescued by Ybb on the Y chromosome.

Originally identified as snRNA but Mount says probably bit of ribosomal RNA.

X-linked insertions of complete rDNA repeats or rDNA fragments that contain the intergenic spacers (IGS) suppress X-Y non-disjunction and meiotic drive in Xh^-/Y males and sterility of T(Y;A) translocations. The IGS is required for this activity.

The positions of pseudouridine residues within the large subunit ribosomal RNA encoded by bb have been identified.

Transgenic constructs containing different copy numbers of a 240bp repeated sequence in the intergenic spacer region (IGS) of the bb gene differ in their ability to promote X-Y chromosome pairing.

Females of a wild type D.melanogaster population Staket fail to produce viable hybrid males when crossed to Dsim\Lhr males. This phenotype is designated as the Staket phenotype. The agent responsible for this phenomenon is the Staket X chromosome. The Staket phenotype can be suppressed by extra copies of functional D.melanogaster rDNA genes. Results suggest that the rDNA genes from the Staket X chromosome are inefficiently transcribed in the D.melanogaster-D.simulans hybrids.

Mutations show strong interactions with high and low selection lines, abdominal and sternopleural bristle numbers are affected. Results suggest bb is a candidate for bristle number quantitative trait loci (QTL) in natural populations or is in the same genetic pathway.

16S and 12S RNA is concentrated at the posterior pole of early embryos suggesting that germ plasm and functional germ cells can form in the absence of high levels of 16S and 12S RNA.

Methidiumpropyl-EDTA.Fe(II) and EDTA.Fe(II) are used to investigate the structure of ribosomes. Regions of 18S and 28S ribosomal RNAs that are accessible to EDTA.Fe(II) and EDTA.Fe(II) are located almost exclusively within expansion segments, results provide information about the overall tertiary structure of rRNA in ribosomes.

bb alleles do not magnify in a closed X chromosome, but a spontaneous ring opening restores normal ring magnification. Results provide strong evidence that the elementary magnifying event is unequal sister chromatid exchange and can be interpreted in the framework of an inducible rDNA-specific recombination system as the basis of ribosomal gene magnification.

60kb repeats located in the distal heterochromatin of the X chromosome have been cloned. These regions, designated as SCLRs, are comprised of the following types of repeated elements: SteXh, copia-like elements (mdg1 elements, aurora-elements and GATE elements), LINE-elements (G-elements and R1-elements), and bb fragments. There are approximately 9 SCLR copies per haploid genome, with a twofold variation in copy number between different fly stocks.

Existing polymorphisms within the internal transcribed spacers (ITS) of rDNA demonstrate there is a higher rate of intrachromosomal exchange than interchromosomal exchange so ITS variants become fixed within a given chromosomal lineage.

DNA sequencing and temperature-gradient gel electrophoresis of the internal transcribed spaces (ITS) between the rDNA genes demonstrate there are three polymorphic sites that are in the process of homogenization.

The internal transcribed spacer regions of the bb locus of a number of Drosophila species have been analysed and compared.

The distribution of rABP50, rABP70 and His1 protein on the 'Alu-repeat' DNA in the non-transcribed spacer of the ribosomal repeat (bb) has been mapped.

Two scaffold attachment regions (SARs) were identified in the rDNA that define two possible loops containing the sequence coding for the 18S rRNA and part of that coding for the 28S rRNA. Sequences identified on the basis of being able to promote extrachromosomal replication in yeast were found to co-map with the SARs. Topological correlation demonstrated between SARs, ARSs and a chromosomal replication origin suggests the physical association of the replication origin with the nuclear substructure.

The level of 18S RNA (encoded by the bb locus) remains fairly constant throughout the D.melanogaster life span.

Stimulation of Drosophila cells by serum of TPA treatment results in increased rRNA transcriptional activity present in nuclear extracts. Enhanced PolI-specific activity requires sequences between -150 and -34 for the effect to be observed.

Maternal 28S rRNA localises to the pole region of the embryo.

Psoralen cross-linking studies reveal that the Hsp70A and 18S rRNA DNA is wound with a significant level of superhelical tension irrespective of state of transcriptional activation.

Tritiated thymidine incorporation experiments indicate that the basis of rDNA magnification is unequal sister chromatid exchange in the rDNA, mediated by an exchange-prone repair system.

The addition of B.thuringiensis supernatant to D.melanogaster culture medium makes possible the detection of modification in X ribosomal DNA content between two wild type Oregon R lines. Variations observed between the two lines lead to the hypothesis that modification in the X rDNA content are not rare events.

Nuclear run-on assays are used to demonstrate that the transcription of rRNA genes by RNA Pol I is rapidly increased by a phorbol ester and serum.

The fraction of bb repeats containing R1-element and/or R2-element sequences has been determined for a number of D.melanogaster strains.

A P element containing X linked rRNA genes, that maps to the intergenic spacer, is used as a starting point for generating internal deletions within the rDNA to assay the effect on XY meiotic pairing.

X-linked insertions of bb deletion fragments are actively transcribed in testes and are capable of stimulating X-Y disjunction. None are capable of forming a nucleolus.

Two lines of Oregan R differ in degree of resistance of the females to the lethal effect of high temperature and to Bacillus thurigeiensis beta-exotoxin, an inhibitor of the nucleolar RNA polymerase. The resistant line came from an Oregan R population subjected over several generations to increased temperature, while the other line, was derived from the parental stock. Twofold variation was observed in the total number of ribosomal genes between the two lines, with the resistant having the higher number. This variation applied to most ribosomal units, including the active ones. Additive variations in specific unit types between the two lines indicate that modifications to the rDNA content are not rare events.

Attempts were made to quantify correlations between rDNA gene copy number and rDNA spacer length in Y-chromosome replacement lines, to detect subtle variation in bristle phenotypes and developmental rates. Such correlations were found, suggesting that the extant molecular variation in Y-linked rDNA can have at most small selective effects.

A comparative analysis of the primary and secondary structure of 28S rRNA expansion segments suggests that the evolution of these segments is a balance between the homogenization of new mutations by unequal crossing-over and a combination of selection against some mutations and selection for subsequent compensatory mutations.

The evolutionary forces that determine the rRNA gene copy number can be identified using estimates of the naturally occurring distributions of rRNA gene copy numbers on the X and Y chromosomes. The distribution is skewed, a long tail toward high copy numbers, it fits a population genetic model that incorporates natural selection and posits three different types of exchange events: sister-chromatid exchange, intrachromatid exchange and interchromosomal crossing-over. Adequate fits of the model were found indicating that either natural selection also eliminates chromosomes with a high copy number, or that the rate of intrachromatid exchange exceeds the rate of interchromosomal exchange.

A biochemical phylogeny of the subgenus Sophophora has been constructed using RNA sequencing to assess the relationship among species. Results show that the branching of willistoni and saltans groups of the subgenus is very ancient and probably predates that of the subgenus Drosophila. The other groups and subgroups are clustered into three main lineages: the melanogaster and oriental subgroups, the montium subgroup and the ananassae subgroup of melanogaster (with the fima and obscura groups).

The rate of evolution of compensatory substitution in the D1 and D2 variable domains of the large rRNA subunit is close to that predicted by a simple model of compensatory substitution through slightly deleterious or slightly advantageous G-U pairs. Base substitutions were scored in 82 related Drosophila species. In all locations where a G-C to A-U compensatory base change occurred, a G-U pair has been observed in one or several species.

Recombination of the nucleolus organiser region (NO) by X chromosome inversion onto the In(1)w^m51b and In(1)w^m4 chromosomes evokes w variegation.

The chromatin structure of the bb has been studied using proteins that crosslink to DNA so histone contacts can be investigated.

240 bp repeat units, clustered in tandem arrays within the rDNA nontranscribed spacer region, include sites of RNA PolI-dependent transcription initiation and elements that stimulate the rate of transcription from the downstream pre-rRNA promoter. Recombinant constructs indicate that activating spacer elements are confined to a region of 70 bp. Spacer and gene promoters are functionally interchangeable as activating units.

Major type I and, minor type I and type II insert containing repeats are disproportionately underreplicated in polytene rDNA. "In^-" repeats, rDNA with an unusually long NTS that lacks either insert type, have a unique localization in the distal portion of the X nucleolus organizer region or the centric heterochromatin and are shown to be preferentially replicated in polytene rDNA.

The promoter region displays a significantly higher level of variation than other regions in the rDNA unit, such as in the 18S. Polymorphisms show different levels of homogenization within the rDNA unit spacer repeats.

Recombination maps of ribosomal arrays have been determined: results demonstrate that the spacer regions are of different lengths and vary in distribution, and reciprocal recombination between rDNA arrays is frequently unequal.

Study of ribosome subunit to polysome ratios in male accessory gland cells suggests that eukaryotic cells may regulate ribosome synthesis in response to the number of free versus translating polysomal ribosomes.

Circular DNA molecules carrying the 240bp repeats of the rDNA intergenic spacer are complete repeats that exhibit no differences in nucleotide sequences with regard to their genomic counterparts.

The slowly evolving sequences within the rDNA promoter region, external transcribed spacers and 5' upstream sequences, have been identified.

Some ribosomal genes interrupted by Type I insertions are functional.

Genetic markers flanking rDNA regions and molecular markers within the rDNA have been used to estimate the frequencies of X-X exchange and X-Y exchange within rDNA tandem arrays. Results demonstrate that reciprocal recombination alone cannot explain the observed variation within and between the rDNA arrays on the two sex chromosomes in natural populations.

Nucleolar organizing activity is an intrinsic property of rDNA or its products. An rDNA gene can be transcribed at a high rate when inserted into chromosomal sites other than the nucleolar organizer. Structures that morphologically, molecularly and functionally resemble the endogenous nucleoli are associated with four sites of rDNA insertion. Thus tandem repetition and heterochromatic localization are not required for rRNA gene function.

G-elements are often inserted into the nontranscribed spacer (NTS) of the rDNA units encoded by bb.

rRNA synthesis rates differ causing the bobbed mutant phenotypes.

In laboratory stocks, bb mutants may arise spontaneously or inadvertently while selecting for mutagen-induced mutations at other loci. bb mutations may be induced at high frequency by carcinogenic hydrocarbons such as 7,12-dimethyl benz^αanthracine (DMBA) (Fahmy and Fahmy, 1969; 1970) or multifunctional alkylating agents such as triethylenemelamine (Tartof). Mutations of the X chromosome bb locus may be specifically induced genetically in four different ways. First, alterations of the X chromosome bb locus may occur bb in males or females carrying the aberrant chromosome Ybb^-. These are high frequency (10^-2-10^-1) events and may be observed as either stable reversions from bb to bb⁺ (magnification: Ritossa, 1968; Komma and Endow, 1986) or as mutations (10^-3-10^-2) from bb⁺ to bb or from bb to bb^l (reduction: Tartof, 1973; Tartof, 1974; Locker and Prud'homme, 1973). It has been suggested that both magnification and reduction may be the result of unequal sister-chromatid exchanges occurring at the X chromosome bb locus in the germ line of X/Ybb^- males (Tartof, 1974); evidence for this is from studies of ring-X bb chromosomes (Endow, Komma and Atwood, 1984); alternatively, a model of excision and reintegration of circular molecules rDNA has been proposed by Ritossa (1972). C(1)RM stocks carrying Ybb^- accumulate modifiers that suppress the bb phenotype (Marcus, Zitron, Wright and Hawley, 1986). Second, in males carrying mei-41, bb⁺ mutates to bb at a frequency of 10^-3 - 10^-2 (Hawley and Tartof, 1983a). mei-41 does not induce reversions of bb to bb⁺ as does Ybb^- nor does it induce bb mutations on the Y. Third, when males carrying certain XY chromosomes are mated to females heterozygous for Rex, free Y chromosomes carrying bb mutants are generated at high frequency (10^-2; Robbins, 1981). Fourth, hybrid dysgenic crosses may also generate bb (Thompson and Woodruff, 1980). Despite such high frequency genetic mutations, homozygous stocks of bb², bb⁴, bb⁶ and bb⁸ have been maintained for 10 years with no evidence of reversions (Tartof). Unless otherwise stated, the origin of most bb mutations is unclear. Exchange between Xh and the Y chromosome at the bobbed locus results in YSXh. and X.YL products that arise at a frequency of about 2 x 10^-4 (for review, see Lindsley, 1955; Hawley and Tartof, 1983a). Orientation of the X rDNA cluster has no effect on the frequency of exchange (Maddern, 1981). Similar events occur in females (Williamson and Parker, 1976). Recombination events involving rDNA sequences of X chromosomes and X and Y chromosomes investigated using restriction-fragment-length polymorphisms (Williams, Kennison, Robbins and Strobeck, 1989).

Three phenotypes are associated with bb mutants: thinning and shortening of bristles, etching of the abdomen, and, in extreme cases, lethality. Of these phenotypes, bristle size and lethality are the most reliable. These phenotypes are somewhat variable from fly to fly and the bristle abnormality may be obscured by such mutations as f, sn and ty to name a few. bb^-/0 males and bb^-/In(1)sc^4Lsc^8R females have phenotypes similar to, but more extreme than, that of homozygous females. bb^-/Y males are wild type, owing to presence of a normal allele of bb in YS (Ybb); bb^-/bb^-/Y females are similarly normal in phenotype. The rate of rRNA synthesis is reduced in bb (FBrf0021411; FBrf0027525; FBrf0027236).

The bb locus encodes the major (18S and 28S) ribosomal RNAs and is the nucleolus organiser (FBrf0017870). In D.melanogaster there are two such loci, one, bb, in the heterochromatin of the X chromosome, the other, Ybb, on the YS chromosome arm. The rRNA encoding genes form large tandem arrays at both loci, and mutant phenotypes result from complete or partial loss of these. Ritossa, Atwood and Spiegelman (FBrf0017870) suggested the bb mutant phenotypes result from reduced protein synthesis.

Source for merge of: bb snRNA-a

Source for merge of: bb flex

"flex" probably corresponds to an allele of bb.

Mutations in "flex" correspond to mutations in the bb locus; lethality of "flex" mutant females is caused by a defect in the functioning of the bb locus on the X chromosome, since this defect is complemented by the corresponding wild-type Ybb locus on the Y chromosome.

Many independent occurrences of bb have been recovered and designated without a superscript; consequently, alleles designated as bb are often unrelated. Given the propensity for bb alleles to change spontaneously and the ambiguities of labeling, it is unlikely than any particular bb stock contains the original bb¹ allele (bb⁵ of Sturtevant). The same arguments apply to Ybb originally described by Bridges.